Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
This study is investigating a new administration schedule of Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine, Prednisone (R-CHOP) chemotherapy for participants with Diffuse
Large B-Cell Lymphoma (DLBCL), focusing on an underserved elderly population (aged 75 and up;
certain participants 70-74 may be eligible) that is often excluded from clinical trials.
Participants can expect to be on study for 2.5 years (treatment for 6 months and 2 years of
post treatment follow-up).
Christopher Fletcher, MD
All
70 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03943901
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Inclusion Criteria:
• Signed and dated informed consent document indicating that the participant (or legally
acceptable representative) has been informed of all pertinent aspects of the trial
• All patients age ≥75 years and participants aged 70-74 years who are determined to be
unfit or frail by Cumulative Illness Rating Score-Geriatrics (CIRS-G) scale
• For participants aged 70-74 years: CIRS-G score with 5-8 comorbid conditions
scored 2 or ≥1 comorbidity scored 3-4. CIRS-G score is to be reviewed by the
study PI prior to enrollment.
• Newly diagnosed, untreated, biopsy proven CD20 positive DLBCL (including high grade
B-cell lymphoma & T-cell/histiocytic rich large B-cell lymphoma). Participants with
discordant bone marrow (i.e. involved by low-grade/indolent NHL) are eligible.
Participants with transformed DLBCL from underlying low-grade disease are eligible.
Participants with composite DLBCL and concurrent low-grade lymphoma are eligible.
• Copy of pathology report must be sent to coordinating site to confirm diagnosis
for eligibility
• Participants with prior treatment for low grade NHL with non-anthracycline based
regimens are eligible
• Measurable disease by PET/CT or Bone Marrow (BM) biopsy prior to enrollment
• Left ventricular ejection fraction ≥50% by resting echocardiography or resting
Multi-gated acquisition (MUGA) scan
• Karnofsky Performance Score ≥50
• Ann Arbor Stage II bulky, III, or IV disease
• Minimum life expectancy greater than 3 months
• Negative HIV test
• For participants with hepatitis B virus antigen (HbsAg) or core antibody (HbcAb)
seropositivity, participants must have a negative Hep B viral load and an appropriate
prophylaxis plan must be in place during chemotherapy therapy treatment. For all
participants that have Hep B core antibody positive, they should take entecavir
prophylaxis (0.5 mg PO daily) until 1 year from completion of chemotherapy. Hep B
viral load should be checked on these participants prior to starting chemotherapy and
every 3 months thereafter if initial Hep B viral load is negative (+/- 1 week if
chemotherapy cycle is delayed). If Hep B viral load is positive, Hepatology or
Identification (ID) referral is recommended, and hepatitis B virus (HBV) viral load
should be checked monthly
• For participants with hepatitis C Ab (HbcAb) positivity, a viral load must be checked
and be negative for enrollment
• Intrathecal chemotherapy for central nervous system prophylaxis only can be given at
the discretion of the primary oncologist
Exclusion Criteria:
• History of previous anthracycline exposure
• Central Nervous System (CNS) or meningeal involvement at diagnosis
• Creatinine Clearance <25 mL/min by body surface area (BSA)-adjusted Cockroft-Gault
• Poor hepatic function, defined as total bilirubin concentration greater than 3.0 mg/dL
or transaminases over 4 times the maximum normal concentration, unless these
abnormalities are felt to be related to the lymphoma.
• Pulmonary dysfunction defined as >2 L of oxygen required by nasal cannula to maintain
peripheral capillary oxygen saturation (SpO2) ≥90% unless felt to be related to
underlying lymphoma.
• Myocardial Infarction within 6 months of enrollment
• Active, uncontrolled infectious disease
• Known concurrent bone marrow malignancies (e.g. myelodysplastic syndrome) or poor
bone-marrow reserve, defined as neutrophil count less than 1.5×10⁹/L or platelet count
less than 100×10⁹/L, unless caused by bone-marrow infiltration with lymphoma
• History of a second concurrent active malignancy or prior malignancy which required
chemotherapy treatment within the preceding 2 years
• Treatment with any investigational drug within 30 days before the planned first cycle
of chemotherapy
• Unable or unwilling to sign consent
Non-Hodgkin's Lymphoma, Lymphoma, Diffuse Large B Cell Lymphoma, DLBCL, Cancer
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
This phase I trial studies the safety of transplantation with a haploidentical donor
peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with
the immunomodulating drug, Zoledronate, given in the post-transplant period to treat
pediatric patients with relapsed or refractory hematologic malignancies or high risk solid
tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:
• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
• Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation;
and
• The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi •EIA (Chagas)
Exclusion Criteria:
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Ill-Defined Sites, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma
Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
This is a Phase I/II, multicenter, open-label, dose escalation/dose-expansion study to
evaluate the tolerability, safety, and the maximum tolerated dose (MTD) of ruxolitinib when
given with fixed dose nivolumab in patients with relapsed or refractory classical Hodgkin
lymphoma (cHL).
Vaishalee Kenkre, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03681561
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Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1 or 2.
• Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or
refractory •historical biopsy at last relapse is acceptable. NOTE: a repeat biopsy is
not required for Phase I if the historical biopsy was performed at the most recent
relapse, without remission in between. A fresh biopsy is not required for Phase II.
• Presence of radiographically measurable disease (defined as the presence one or more ≥
1.5 cm lesions, as measured in the longest dimension by PET/CT) within 4 weeks of
study registration.
• Prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others) and
subsequent progressive disease, stable disease or mixed response
• Failed at least 2 prior therapies including cytotoxic chemotherapy including ABVD or
similar, autologous transplantation, brentuximab vedotin, allogenic transplantation
without active graft versus host disease Note: Patients who are eligible and willing
to undergo autologous transplant should not be enrolled on this trial
• Prior cancer treatment must be completed at least 14 days prior to registration and
the patient must have recovered from all reversible acute toxic effects of the regimen
(other than alopecia) to ≤Grade 1 or baseline. Radiation therapy must be completed at
least 7 days prior to registration.
• Absolute Neutrophil Count ≥ 1000/μL
• Platelets ≥ 75,000/μL (or ≥50,000/mm3 if known BM involvement)
• Calculated creatinine clearance ≥ 40 cc/min using the Cockcroft-Gault formula
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• Females of childbearing potential must have a negative serum pregnancy test within 7
days prior to registration. NOTE: Females are considered of child bearing potential
unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
12 consecutive months
• Males who are sexually active with partners of child-bearing potential must be willing
to abstain from heterosexual activity or adhere to contraception from the time of
written consent until 7 months after treatment discontinuation.
• Patient must provide voluntary written informed consent prior to the performance of
any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
• Inability or unwillingness to swallow oral medication or any condition that precludes
the administration and/or absorption of oral medications
• A life-threatening illness, medical condition or organ system dysfunction, which in
the investigator's opinion, could compromise the patient's safety, interfere with the
metabolism of study drugs, or put the study outcomes at undue risk
• Active central nervous system (CNS) involvement by lymphoma
• Uncontrolled cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, or myocardial infarction or any class 3 or 4 cardiac disease
as defined by the New York Heart Association Functional Classification
• Concomitant therapy with immunosuppressive agents, including systemic corticosteroids
(doses ≤ 10 mg/day prednisone or equivalent are permitted).
• Has a history of autoimmune disease now or in past 3 years such as hepatitis,
nephritis, hyperthyroidism, interstitial lung disease or colitis except vitiligo or
alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months of registration are eligible for this trial.
• Active Hepatitis B or C infection (defined as a positive Hepatitis B surface antigen
(Ag) or detectable viral load by PCR). NOTES: Hepatitis B and C testing is required.
Patients with positive Hepatitis B Ag may enroll if PCR is negative. Suppressive
antiviral therapy should be considered for these patients as clinically indicated.
• Currently active, clinically significant hepatic impairment Child-Pugh class B or C
• Currently receiving a strong CYP3A4 Inhibitor (such as but not limited to boceprevir
clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole,
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,
saquinavir, telaprevir, telithromycin, voriconazole) or Fluconazole >200 mg/day.
Washout period of 1 week is required.
• History of stroke or intracranial hemorrhage within 6 months of study registration
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)
The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or
refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain
tumors for which there are no standard treatment options with curative potential.
Nicholas Pytel, DO
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g.,
neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain
tumors that are clinically or radiographically suspected to be relapsed, refractory,
or recurrent for which there are no standard treatment options with curative
potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll
without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky
performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to
study registration, and, unless deemed medically necessary, no transfusions are
allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study
registration, and, unless deemed medically necessary, no transfusions are allowed
between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60
ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at
least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have
availability or ability to collect an autologous hematopoietic stem cell back-up
product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+
cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the
initiative and means to be compliant with the protocol.
Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a
lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron
emission tomography (PET) positive may be enrolled at the investigator's discretion,
even if not associated with a measurable lesion of at least 10 mm. Patients with
neuroblastoma who have detectable disease may enroll provided they meet the
requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic
treatments for brain metastases prior to enrollment; by investigator assessment be
considered stable with no new signs or symptoms for at least 1 month, and on a stable
dose of steroids (unchanged for three weeks prior to registration or on a steroid
tapering regimen).
Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging
sequence.
• Patients with previously known neurological deficits must be clinically stable at time
of enrollment and able to complete all study related procedures. Patients with
documented or newly diagnosed neurological deficits will be enrolled at the
investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable
(unchanged for three weeks prior to registration) or on a steroid tapering regimen.
Initiation of steroids per routine care immediately prior to CLR 131 dosing is
acceptable.
Exclusion Criteria:
• Patients receiving active treatment for central nervous system metastases or those
that are likely to require active treatment during anticipated participation in this
trial. Patients with stable brain metastases treated with steroids may enroll at the
investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless
previously treated with surgery, systemic therapy, or radiotherapy with the patient
neurologically stable. Patients with metastatic brain tumors that have been previously
treated are allowed, provided the patient is neurologically stable (determined at the
investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain
types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to
skull-based metastases is not considered craniospinal radiation for the purposes of
this study]), at least 3 months must have elapsed. No washout is required for
palliative focal radiation. NOTE: Patients participating in non-interventional
clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a
cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in
this trial, are not eligible.
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to
children by their health care provider, act in the bodies of children and young adults in
hopes to find the most safe and effective dose for children. The primary objective of this
study is to evaluate the PK of understudied drugs currently being administered to children
per SOC as prescribed by their treating provider.
Maria Stanley
All
0 Years to 20 Years old
NA
This study is also accepting healthy volunteers
NCT04278404
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Inclusion Criteria:
1. Participant is < 21 years of age
2. Parent/ Legal Guardian/ Adult Participant can understand the consent process and is
willing to provide informed consent/HIPAA:
3. (a) Participant is receiving one or more of the study drugs of interest at the time of
enrollment or (b) Participant is NOT receiving one or more of the study drugs of
interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
1. Participant has a known pregnancy
Below exclusion criteria apply only to:
Participants receiving one or more of the study drugs of interest at the time of
enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for
details on enrollment cohort specifications and additional eligibility criteria)
2. Has had intermittent dialysis within previous 24 hours
3. Has had a kidney transplant within previous 30 days
4. Has had a liver transplant within previous 1 year
5. Has had a stem cell transplant within previous 1 year
6. Has had therapeutic hypothermia within previous 24 hours
7. Has had plasmapheresis within the previous 24 hours
8. Has a Ventricular Assist Device
9. Has any condition which would make the participant, in the opinion of the
investigator, unsuitable for the study
Coronavirus Infection (COVID-19), Pulmonary Arterial Hypertension, Urinary Tract Infections in Children, Hypertension, Pain, Hyperphosphatemia, Primary Hyperaldosteronism, Edema, Hypokalemia, Heart Failure, Hemophilia, Menorrhagia, Insomnia, Pneumonia, Skin Infection, Arrythmia, Asthma in Children, Bronchopulmonary Dysplasia, Adrenal Insufficiency, Fibrinolysis, Hemorrhage, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder, Down Syndrome, Other
Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all
pediatric and adult participants exposed to Gene-modified (GM) T cell therapy participating
in a previous Celgene sponsored or Celgene alliance partner sponsored study.
Participants who received at least one GM T cell infusion will be asked to enroll in this
LTFU protocol upon either premature discontinuation from, or completion of the prior parent
treatment protocol.
Natalie Callander, MD
All
Not specified
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03435796
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Inclusion Criteria:
• Received at least one gene-modified (GM) T-cell infusion in a previous Celgene
sponsored or Celgene alliance partner-sponsored study, and have discontinued, or
completed the post-treatment follow-up period in the parent treatment protocol, as
applicable.
• Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form
prior to any study-related assessments/procedures being conducted.
Exclusion Criteria:
Not Applicable
Other protocol-defined inclusion/exclusion criteria apply
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction
chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial will also study the outcomes of patients with mixed phenotype acute
leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk
ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
Induction and Consolidation. This part will collect information on the leukemia, as well as
the effects of the initial treatment, to classify patients into post-consolidation treatment
groups. On the second part of this study, patients with HR B-ALL will receive the remainder
of the chemotherapy cycles (interim maintenance I, delayed intensification, interim
maintenance II, maintenance), with some patients randomized to receive inotuzumab. The
patients that receive inotuzumab will not receive part of delayed intensification. Other aims
of this study include investigating whether treating both males and females with the same
duration of chemotherapy maintains outcomes for males who have previously been treated for an
additional year compared to girls, as well as to evaluate the best ways to help patients
adhere to oral chemotherapy regimens. Finally, this study will be the first to track the
outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed
Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Kenneth Desantes, M.D.
All
1 Year to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03959085
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Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B-LLy patients may directly
enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on
central confirmatory testing to have B-ALL must meet the B-ALL criteria above
(age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL
stratum before the end of induction.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• Central nervous system (CNS) status must be determined prior to enrollment based on a
sample obtained prior to administration of any systemic or intrathecal chemotherapy,
except for steroid pretreatment and cytoreduction. It is recommended that intrathecal
cytarabine be administered at the time of the diagnostic lumbar puncture. This is
usually done at the time of the diagnostic bone marrow or venous line placement to
avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic
chemotherapy must begin within 72 hours of this intrathecal therapy.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment and steroid cytoreduction or the
administration of intrathecal cytarabine, patients must not have received any prior
cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any
cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of
systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in
treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or
B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as
blinatumomab, may induce changes in the body's immune system and may interfere with the
ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine,
dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine,
mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to
stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate.
Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving
blinatumomab and combination chemotherapy may work better than combination chemotherapy alone
in treating patients with B-ALL. This trial also assigns patients into different chemotherapy
treatment regimens based on risk (the chance of cancer returning after treatment). Treating
patients with chemotherapy based on risk may help doctors decide which patients can best
benefit from which chemotherapy treatment regimens.
Kenneth Desantes, M.D.
All
365 Days to 31 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03914625
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Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
(Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
(performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell
count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion
for diagnosis should be analogous to B-ALL. For tissue processed by other means
(i.e., paraffin blocks), the methodology and criteria for immunophenotypic
analysis to establish the diagnosis of B-LLy defined by the submitting
institution will be accepted (diagnostic biopsy for B-LLy must be performed
within 14 days prior to enrollment).
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patient must not have secondary ALL that developed after treatment of a prior
malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
history of transient myeloproliferative disease (TMD) are not considered to have had a
prior malignancy. They would therefore be eligible whether or not the TMD was treated
with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion
criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in
the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to
the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the
DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
to administration of any systemic or intrathecal chemotherapy, except for steroid
pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% •25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Down Syndrome, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
This phase II trial studies how stopping tyrosine kinase inhibitors will affect
treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the
level of disease is very low, it's called molecular remission. TKIs are a type of medication
that help keep this level low. However, after being in molecular remission for a specific
amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet
known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid
leukemia in chronic phase continue or re-achieve molecular remission.
Kenneth Desantes, M.D.
All
up to 25 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03817398
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Inclusion Criteria:
• Patient must have been diagnosed with CML-CP at < 18 years of age.
• Patient must have histologic verification of CML-CP at original diagnosis
• Patient must be in molecular remission (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1
as measured using the International Scale (IS) by RQ-PCR for >= 2 consecutive years at
the time of enrollment
• Please note: The lab evaluating disease status and molecular response for this
study must be College of American Pathology (CAP) and/or Clinical Laboratory
Improvement Amendments (CLIA) certified (United States [US] only), sites in other
countries must be certified by their accredited authorities. All labs must use
the International Scale guidelines with a sensitivity of detection assay =< 0.01%
BCR-ABL1 and be able to report results in =< 2 weeks
• Patient must have received any TKI for a minimum of 3 consecutive years at time of
enrollment
• Patient agrees to discontinue TKI therapy
• REGULATORY REQUIREMENTS
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
• ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
• Age >= 8 years at the time of enrollment
• Ability to understand English or Spanish
• Cognitive ability to complete instruments according to the primary team
• ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
• Patient must be 5 years or older at the time of enrollment
• English-, French- or Spanish-speaking
• No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down
syndrome, Fragile X, William syndrome, mental retardation)
• No significant visual or motor impairment that would prevent computer use or
recognition of visual test stimuli
Exclusion Criteria:
• Known T3151 mutation
• Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive
(+) cells at any time prior to enrollment that include "major route" abnormalities
(second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or
abnormalities of 3q26.2
• History of accelerated phase or blast crisis CML
• Female patients who are pregnant
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained
The investigators want to study if lower doses of chemotherapy will help babies with SCID to
achieve good immunity with less short and long-term risks of complications after
transplantation. This trial identifies babies with types of immune deficiencies that are most
likely to succeed with this approach and offers them transplant early in life before they get
severe infections or later if their infections are under control. It includes only patients
receiving unrelated or mismatched related donor transplants.
The study will test if patients receiving transplant using either a low dose busulfan or a
medium dose busulfan will have immune recovery of both T and B cells, measured by the ability
to respond to immunizations after transplant. The exact regimen depends on the subtype of
SCID the patient has. Donors used for transplant must be unrelated or half-matched related
(haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance
of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T
cells removed, using a newer, experimental approach of a well-established technology. Once
the stem cell transplant is completed, patients will be followed for 3 years. Approximately
9-18 months after the transplant, vaccinations will be administered, and a blood test
measuring whether your child's body has responded to the vaccine will be collected.
Kenneth Desantes, M.D.
All
0 Years to 2 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03619551
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Inclusion Criteria:
1. Infants with SCID, either typical or leaky or Omenn syndrome.
1. Typical SCID is defined as either of the following
• Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or
very low T cell function (<10% of lower limit of normal) as measured by response
to phytohemagglutinin OR
• Presence of maternally derived T cells
2. Leaky SCID is defined as the following
• Absence of maternally derived T cells
• AND either one or both of the following (i, ii): i) <50% of lower limit of normal T
cell function as measured by response to PHA OR <30% of lower limit of normal T cell
function as measured by response to CD3 ii) Absent or <10% of lower limit of normal
proliferative responses to candida and tetanus toxoid antigens (must document post
vaccination or exposure for this criterion to apply)
• AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter
ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of
age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+
or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
3. Omenn syndrome • Generalized skin rash
• Maternal lymphocytes tested for and not detected.
• >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of
age)
• Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to
antigens (Candida, tetanus) to which the patient has been exposed IF:
Proliferation to antigen was not performed, but at least 4 of the following 8
supportive criteria, at least one of which must be among those marked with an
asterisk (*) below are present, the patient is eligible as Omenn Syndrome.
1. Hepatomegaly
2. Splenomegaly
3. Lymphadenopathy
4. Elevated IgE
5. Elevated absolute eosinophil count
6. *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload
report)
7. *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or
SI < 30
8. *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells
below the lower level of normal
2. Documented mutation in one of the following SCID-related genes
a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1,
RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a
suitable donor and graft source
1. Haploidentical related mobilized peripheral blood cells
2. 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor
mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment
Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:
For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks
6. Adequate organ function defined as:
1. Cardiac:
Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥
26% by echocardiogram.
2. Hepatic:
Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have
been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and
ALT < 5.0 x ULN for age.
3. Renal:
GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated
GFR is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine
clearance or nuclear GFR, and must be > 50 mL/min/1.73 m2.
4. Pulmonary No need for supplemental oxygen and O2 saturation > 92% on room air at sea
level (with lower levels allowed at higher elevations per established center standard
of care).
Exclusion Criteria:
1. Presence of any serious life-threatening or opportunistic infection at time of
enrollment and prior to the initiation of the preparative regimen. Serious infections
as defined below that occur after enrollment must be reported immediately to the Study
Coordinating Center, and enrollment will be put on hold until the infection resolves.
Ideally enrolled subjects will not have had any infection. If patients have
experienced infections, these must have resolved by the following definitions:
a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site must be negative and patient has completed appropriate
course of antibacterial therapy (typically at least 10 days).
ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical
signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course
of antibacterial therapy (typically at least 10 days).
iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution
of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed
appropriate course of antibacterial therapy (typically at least 10 days). If possible,
radiographic resolution should also be demonstrated.
b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site is negative and patient has completed appropriate course of
antifungal therapy (typically at least 14 days). The patient may be continued on
antifungal prophylaxis following completion of the treatment course.
c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen
requirement, etc.) and patient has completed appropriate course of therapy (typically
at least 21 days). If possible, radiographic resolution should also be demonstrated.
The patient may be continued on prophylaxis following completion of the treatment
course.
d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must
be re-tested and are negative.
ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete
resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible,
radiographic resolution should also be demonstrated.
2. Patients with HIV or HTLV I/II infection will be excluded.
SCID, Other Hematopoietic, Unknown Sites, Hematologic cancers, other
Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma
This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide,
or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma
that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy
with obinutuzumab, may induce changes in body's immune system and may interfere with the
ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Biological therapies, such as
lenalidomide, use substances made from living organisms that may stimulate or suppress the
immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such
as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. It is not yet known whether giving
obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work
better in treating patients with grade I-IIIa follicular lymphoma.
Vaishalee Kenkre, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03269669
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Inclusion Criteria:
• Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial
diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on
PET/CT; patients that have involvement with large cell lymphoma are not eligible
• Patients must have a whole body or limited whole body PET/CT scan performed within 42
days prior to registration
• Patients must have bone marrow biopsy performed within 42 days prior to registration
• Patients must have an indication for therapy as determined by the treating
investigator
• All disease must be assessed and documented on the S1608 FDG-PET/CT assessment form
• The intent is to enroll patients with follicular lymphoma (FL) relapsed within 2 years
of completing their first course of chemotherapy (CHOP or bendamustine based therapy)
+ anti-CD20 therapy. Patient is still eligible if he/she received radiation therapy or
anti-CD20 therapy prior to chemoimmunotherapy or if maintenance anti-CD20 therapy was
administered after chemoimmunotherapy
• Patients must have either failed to achieve a complete remission, or must have
relapsed within 2 years after completing CHOP or bendamustine-containing
chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from
the last dose of CHOP or bendamustine; relapsed patients must not have received
any intervening chemotherapy
• Patients must have received only 1 course of chemotherapy, containing at least 3
cycles of CHOP or bendamustine; (note that no minimum dose of bendamustine is
required)
• Patients who received any anti-CD20 antibody therapy prior to CHOP or
bendamustine are eligible
• Patients who additionally received any maintenance anti-CD-20 antibody therapy or
consolidative radioimmunotherapy within 2 years of the last dose of the CHOP or
bendamustine therapy are eligible
• Involved field or involved site radiation is not considered a line of therapy;
examples of eligible prior treatment regimens (note this list is not all
inclusive):
• 1st line rituximab treatment followed years later by bendamustine rituximab
• Bendamustine rituximab x 4 cycles
• 1st line rituximab treatment, 2nd line ibritumomab tiuxetan, followed by
bendamustine bortezomib rituximab x 6 cycles followed by rituximab
maintenance
• Bendamustine obinutuzumab x 3 cycles
• CHOP rituximab x 6 cycles followed by rituximab maintenance
• For all forms of systemic therapy, patients must have completed therapy at least 21
days prior to registration; patients must have completed any radioimmunotherapy at
least 84 days prior to registration; patients prior treatment related toxicities
(except alopecia) must have resolved to grade 1 or less prior to registration
• Patients must have tissue specimens collected prior to registration; patients must be
offered participation in biobanking of residual specimens; with patient consent,
residuals from the mandatory submission(s) will be banked for future research
• Patients must be >= 18 years of age
• All patients must have a Zubrod performance status of 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1,500/mcL within 28 days prior to registration
• Platelets >= 75,000/mcL within 28 days prior to registration
• Patients must have adequate renal function as documented by a calculated creatinine
clearance >= 60 mL/min, within 28 days prior to registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (=< 5 x IULN if
secondary to lymphoma, Gilbert's syndrome, or medication related [e.g., indinavir,
tenofovir, atazanavir]) within 28 days prior to registration
• Direct bilirubin =< 1.5 x IULN (=< 5 x IULN if secondary to lymphoma) within 28 days
prior to registration
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (=<
5 x IULN secondary to lymphoma) within 28 days prior to registration
• Patients must have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan
within 42 days prior to registration with a cardiac ejection fraction >= 45%
• Patients with hepatitis B virus infection must have undetectable hepatitis B virus
(HBV) on suppressive therapy and no evidence of HBV-related hepatic damage; patients
with hepatitis C virus infection are eligible if complete eradication therapy has been
successfully completed, and there is no detectable hepatitis C virus (HVC) or related
hepatic damage; patients with known human immunodeficiency virus (HIV) infection are
eligible if they meet all of the following criteria in addition to the other protocol
eligibility criteria:
• Patient must have no history of acquired immune deficiency syndrome
(AIDS)-related complications, other than a history of low CD4+ T-cell count (<
200/mm^3) prior to initiation of combination antiretroviral therapy; on study
CD4+ T-cell count may not be informative due to leukemia and should not be used
as an exclusion criterion if low
• Patient must be healthy on the basis of HIV disease with high likelihood of near
normal life span were it not for the leukemia
• Patient must have serum HIV viral load of < 200 copies/mm^3
• Patient must be on combination antiretroviral therapy with minimal
pharmacokinetic interactions with study therapy and minimal overlapping clinical
toxicity with protocol therapy; (recommend a regimen of the integrase inhibitor
dolutegravir combined with either disoproxil fumarate/emtricitabine or
dolutegravir combined with tenofovir alafenamide/emtricitabine)
• Protease inhibitors and once daily formulations containing cobicistat are NOT
allowed due to potential pharmacokinetic interactions with leukemia therapy
• Stavudine and zidovudine (AZT) are NOT allowed because of overlapping toxicity
with protocol therapy
• Patients must be able and willing to receive prophylaxis with daily aspirin, low
molecular weight heparin, factor X inhibitors or warfarin if randomized to
lenalidomide; patients unable or unwilling to take any listed prophylaxis are NOT
eligible
• No second prior malignancy is allowed except for adequately treated basal (or squamous
cell) skin cancer, in situ cervical cancer or other cancer for which the patient has
been disease free for three years
• Patients must have a complete history and physical examination within 28 days prior to
registration
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24
hours prior to starting cycle 1 of lenalidomide; further, they must either commit to
complete abstinence (true abstinence is acceptable when this is in line with the
preferred and usual lifestyle of the subject; periodic abstinence [e.g., calendar,
ovulation, symptothermal or post ovulation methods] and withdrawal are not acceptable
methods of contraception) from heterosexual intercourse or begin TWO acceptable
methods of birth control: one highly effective method and one additional effective
method AT THE SAME TIME, at least 28 days before starting lenalidomide; while taking
lenalidomide, during dose interruptions, and for at least 28 days after the last dose
of lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to
use a latex condom during sexual contact with a FCBP, even if they have had a
successful vasectomy; a FCBP is a female who: 1) has achieved menarche at some point;
2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been
naturally postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had menses at
any time in the preceding 24 consecutive months); all patients must be counseled by a
trained counselor every 28 days about pregnancy precautions and risks of fetal
exposure; NOTE: patients not randomized to receive lenalidomide will not be required
to undergo serial pregnancy testing or lenalidomide counseling after registration
• Patients must have lactate dehydrogenase (LDH) and beta-2-microglobulin collected
within 28 days prior to registration
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
Exclusion Criteria:
• Patients must not have clinical evidence of central nervous system involvement by
lymphoma since the proposed treatment strategies are not designed to address central
nervous system (CNS) involvement adequately; if performed, any laboratory or
radiographic tests performed to assess CNS involvement must be negative
• Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213652
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Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the
presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment
with other ALK inhibitors is permitted given that at least 5 half-lives or 21
days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is
currently no available information regarding human fetal or teratogenic toxicities;
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment and for one week after the
last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the
end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03155620
Show full eligibility criteria
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Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects
with low risk germ cell tumors for recurrence after their tumor is removed. When the germ
cell tumors has spread outside of the organ in which it developed, it is considered
metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. The trial studies
whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic
standard risk germ cell tumors.
Kenneth Desantes, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT03067181
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Inclusion Criteria:
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and
stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I
germ cell tumor; for the standard risk arms, patients must be newly diagnosed with
metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary
extracranial germ cell tumor in any of the categories outlined below is required of
all patients at enrollment except for those who were initially diagnosed with stage I
non-seminoma malignant GCT and later recur during observation post surgery off study;
for these patients, if elevated tumor markers rise to > 5 x upper limit of normal
(ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is
not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk
sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT);
tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage:
COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC)
testicular stage IA, IB and IS; histology: must contain at least one of the following:
yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular
stage IA IB, and IS; histology: must contain at least one of the following: may
contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) <
11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk;
histology: must contain at least one of the following: yolk sac tumor, embryonal
carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op:
alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age
(years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the
study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components
of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with
other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac
tumor is the only malignant component present, then it must be deemed by the
pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
(mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L) (within 7 days prior to enrollment)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to
enrollment) AND
• Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol
treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL
• Pure immature teratoma COG stage II •IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that
contraindicate the use of bleomycin are ineligible for the standard risk arms of the
trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Hodgkin's Lymphoma, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
This randomized phase III trial studies how well imatinib mesylate works in combination with
two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia
chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to
improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL
when given with strong chemotherapy, but the combination has many side effects. This trial is
testing whether a different chemotherapy regimen may work as well as the stronger one but
have fewer side effects when given with imatinib. The trial is also testing how well the
combination of chemotherapy and imatinib works in another group of patients with a type of
ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL",
and because it is similar to Ph+ ALL, is thought it will respond well to the combination of
agents used to treat Ph+ ALL.
Kenneth Desantes, M.D.
All
1 Year to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03007147
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Inclusion Criteria:
• For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required
diagnostic bone marrow sample has been fulfilled
• For patients who have not previously enrolled on APEC14B1 prior to enrollment on
AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if
marrow sample unavailable) must be available to develop an MRD probe
• In addition, laboratory reports detailing evidence of BCR-ABL1 fusion or
ABL-class fusion must be submitted for rapid central review within 72 hours of
study enrollment
• >= 1 year (365 days) and =< 21 years at ALL diagnosis
• Ph+ (BCR-ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed
phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO]
definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in
situ hybridization (FISH) and/or molecular methodologies
• ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions.
ABL-class fusions are defined as those involving the following genes: ABL1, ABL2,
CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization
(FISH, e.g. using break-apart or colocalization signals probes), multiplex or
singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole
transcriptome or panel-based ribonucleic acid (RNA)-sequencing (e.g. TruSight RNA
Pan-Cancer Panel; Illumina, San Diego, CA, USA or similar)
• Ph+ patients must have previously started Induction therapy, which includes
vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or
other standard cytotoxic chemotherapy
• Ph+ patients have not received more than 14 days of multiagent Induction therapy
beginning with the first dose of vinCRIStine
• Ph+ patients may have started imatinib prior to study entry but have not received more
than 14 days of imatinib
• ABL-class fusion patients must have previously completed the 4 or 5 weeks of
multiagent Induction chemotherapy (Induction IA phase)
• ABL-class fusion patients may have started imatinib during Induction IA, at the same
time of or after the first vinCRIStine dose
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2
• Direct bilirubin =< 2.0 mg/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT interval, QTc < 480 msec
• Note: Repeat echocardiogram and electrocardiogram are not required if they were
performed at or after initial ALL diagnosis, before study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as
follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Exclusion Criteria:
• Known history of chronic myelogenous leukemia (CML)
• ALL developing after a previous cancer treated with cytotoxic chemotherapy
• Active, uncontrolled infection, or active systemic illness that requires ongoing
vasopressor support or mechanical ventilation
• Down syndrome
• Pregnancy and breast feeding
• Female patients who are pregnant since fetal toxicities and teratogenic effects
have been noted for several of the study drugs; a pregnancy test is required for
female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of treatment according to
protocol
• Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart
block
• Prior treatment with dasatinib, or any TKI other than imatinib
Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Leukemia, other, Leukemia
The National Myelodysplastic Syndromes (MDS) Study (MDS)
Multi-center study enrolling patients suspected or newly diagnosed with myelodysplastic
syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) overlap
disorder, or idiopathic cytopenia of undetermined significance (ICUS). Participants will be
followed long term. Clinical data, blood, and tissue samples will be collected to establish a
biorepository to facilitate the study of the natural history of MDS.
Ryan Mattison, MD
All
18 Years and over
III
This study is NOT accepting healthy volunteers
NCT02775383
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Inclusion Criteria:
• Suspected (e.g., persistent unexplained cytopenia, circulating peripheral blasts etc.)
MDS or MDS/MPN overlap disorders and undergoing diagnostic work-up with planned bone
marrow assessments, or diagnosed with de novo or therapy-related MDS within 12 months
of enrollment per the World Health Organization (WHO) criteria1 and undergoing
clinical evaluation and planned bone marrow assessments to confirm MDS or to evaluate
disease status
• Bone marrow aspirate expected to be performed within 1 week of registration, and in
all cases must be performed no later than 4 weeks after enrollment
• Age 18 or older
• If anemic without prior MDS diagnosis, B12 level, serum folate, mean corpuscular
volume (MCV), red cell distribution width (RDW), ferritin, and iron studies (Iron,
total iron-binding capacity (TIBC) test, and percent saturation) must be performed
within prior 6 months.
Exclusion Criteria:
• Prior treatment for MDS at entry and through the time of the entry bone marrow
aspirate
• Treatment with hematopoietic growth factors in prior 6 months
• Diagnosis of a solid tumor or hematologic malignancy within two years prior to
enrollment except for in situ cancer of the skin (basal or squamous cell), cervix,
bladder, breast, or prostate
• Treatment with radiation therapy in the two years prior to registration
• Non-hormonal treatment for malignancy within the two years prior to registration
• Established hereditary bone marrow failure syndrome
• Known primary diagnosis of aplastic anemia, classical paroxysmal nocturnal
hemoglobinuria, amegakaryocytic thrombocytopenic purpura, or large granular lymphocyte
leukemia
• Enrolled in the Connect® MDS/AML Disease Registry (NCT01688011)
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and
safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who
received first-line treatment and are EOC MRD positive. The study will have the following
sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After
tisagenlecleucel infusion, patient will have assessments performed more frequently in the
first month and then at Day 29, then every 3 months for the first year, every 6 months for
the second year, then yearly until the end of the study. Efficacy and safety will be assessed
at study visits and as clinically indicated throughout the study. The study is expected to
end in approximately 8 years after first patient first treatment (FPFT). A post-study long
term follow-up safety will continue under a separate protocol per health authority
guidelines.
Christian Capitini, MD
All
1 Year to 25 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03876769
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Inclusion Criteria:
1. CD19 expressing B-cell Acute Lymphoblastic Leukemia
2. De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC
bone marrow MRD will be collected prior to screening and will be assessed by
multi-parameter flow cytometry using central laboratory analysis.
3. Age 1 to 25 years at the time of screening
4. Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
5. Adequate organ function during the screening period:
A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times
ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total
bilirubin < 4 mg/dL)
E. Adequate pulmonary function defined as:
• no or mild dyspnea (≤ Grade 1)
• oxygen saturation of > 90% on room air F. Adequate cardiac function defined as
LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram
or MUGA within 6 weeks of screening
6. Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks
of standard chemotherapy for first-line B-ALL, defined as 4-drug induction,
Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with
high-dose methotrexate.
Exclusion Criteria:
1. M3 marrow at the completion of 1st line induction therapy
2. M2 or M3 marrow or persistent extramedullary disease at the completion of first-line
consolidation therapy or evidence of disease progression in the peripheral blood or
new extramedullary disease prior to enrollment. Patients with previous CNS disease are
eligible if there is no active CNS involvement of leukemia at the time of screening.
3. Philadelphia chromosome positive ALL
4. Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence
of a hypodiploid clone
5. Prior tyrosine kinase inhibitor therapy
6. Subjects with concomitant genetic syndromes associated with bone marrow failure
states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or
any other known bone marrow failure syndrome. Subjects with Down syndrome will not be
excluded.
7. Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia
with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3
morphology and /or a MYC translocation)
8. Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or
engineered T cell therapy
Other protocol-defined inclusion/exclusion may apply.
Per Health Authorities guidelines for gene therapy medicinal products that utilize
integrating vectors (e.g. lentiviral vectors), long term safety and efficacy follow up of
treated patients is required. The purpose of this study is to monitor all patients exposed to
CAR-T therapied for 15 years following their last CAR-T (e.g. CTL019) infusion to assess the
risk of delayed adverse events (AEs), monitor for replication competent lentivirus (RCL) and
assess long-term efficacy, including vector persistence.
Christian Capitini, MD
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT02445222
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Inclusion Criteria:
• All patients who have received a CAR-T therapy and completed or discontinued early
from a Novartis sponsored treatment protocol that utilized CAR-T cells or from any
CAR-T trial sponsored by the University of Pennsylvania with which Novartis has a
contractual agreement to co-develop the CAR technology.
• Patients who have provided informed consent for the long term follow up study prior to
their study participation .
Exclusion Criteria:
• There are no specific exclusion criteria for this study.
Lymphoid Leukemia, Leukemia, Long Term Safety of Patients Receiving CAR-T in an Eligible Clinical Trial or Managed Access Program
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with
cancer. Gathering health information over time from younger patients with cancer may help
doctors find better methods of treatment and on-going care.
Kenneth Desantes, M.D.
All
up to 25 Years old
N/A
This study is NOT accepting healthy volunteers
NCT02402244
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Inclusion Criteria:
• Enrollment must occur within 6 months of initial disease presentation OR within 6
months of refractory disease, disease progression, disease recurrence, second or
secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome,
Registry and Future Contact components of APEC14B1 any time after they reach age of
majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent
or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology
(ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in
situ) or three "3" (malignant)
• All neoplastic lesions of the central nervous system regardless of behavior,
i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Neuroendocrine tumors including pheochromocytoma
• Melanocytic tumors, except clearly benign nevi
• Ganglioneuromas
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients
who are being screened specifically for eligibility onto a COG (or COG participating
National Clinical Trials Network [NCTN]) therapeutic study, for which there is a
higher upper age limit
• All patients or their parents or legally authorized representatives must sign a
written informed consent and agree to participate in at least one component of the
study; parents will be asked to sign a separate consent for their own biospecimen
submission
• If patients or their parents or legally authorized representatives have not
signed the Part A subject consent form at the time of a diagnostic bone marrow
procedure, it is recommended that they initially provide consent for drawing
extra bone marrow using the Consent for Collection of Additional Bone Marrow;
consent using the Part A subject consent form must be provided prior to any other
procedures for eligibility screening or banking under APEC14B1
Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neuroendocrine Neoplasm, Stromal Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis
The LCH-IV is an international, multicenter, prospective clinical study for pediatric
Langerhans Cell Histiocytosis LCH (age < 18 years).
Margo Hoover-Regan
All
up to 18 Years old
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT02205762
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Inclusion Criteria:
• Stratum I
• Patients must be less than 18 years of age at the time of diagnosis.
• Patients must have histological verification of the diagnosis of Langerhans cell
histiocytosis according to the criteria described in Section 6.1
• Signed informed consent form
• Stratum II
• Patients of Stratum I who have:
• Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
• AD intermediate or worse in non-risk organs or AD better in risk organs after 12
weeks (Initial Course 2)
• Disease progression (AD worse) in non-risk organs at any time during continuation
treatment
• Active disease at the end of Stratum I treatment
• Disease reactivation in non-risk organs at any time after completion of Stratum I
treatment
• Stratum III
• Patients from Stratum I who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD
intermediate in risk organs after week 12 (after Initial Course 2).
• Presence of unequivocally severe organ dysfunction at the above mentioned
evaluation points (hematological dysfunction, liver dysfunction, or both of them)
as
• Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
• PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have
to be fulfilled) AND/OR
• Liver dysfunction (or digestive involvement with protein loss)
• Total protein <55 g/L or substitution dependency
• Albumin <25 g/L or substitution dependency (at least one of the two criteria
to be fulfilled)
• Stratum IV
• Patients from Stratum I or Stratum III who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD
intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I
OR
• AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD
intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
• Presence of unequivocally severe organ dysfunction at the above mentioned
evaluation points (hematological dysfunction, liver dysfunction, or both of them)
as defined in Table XI (see Section 10.3.1).
• Informed consent: All patients or their legal guardians (if the patient is <18
years of age) must sign an Ethics or institutional Review Board approved consent
form indicating their awareness of the investigational nature and the risks of
this study. When appropriate, younger patients will be included in all
discussions in order to obtain assent.
• Adequate organ function: Patients should have adequate hepatic, renal, cardiac
and pulmonary function to undergo reduced intensity HCT based upon local
institutional guidelines, or at a minimum meet requirements noted in eligibility
checklist Appendix A-VIII_1. However, significant hepatic and pulmonary
dysfunction, if secondary to underlying LCH disease activity, will not exclude
patients from protocol enrollment and should be discussed with the National PI
Coordinator and the Coordinating Principal Investigator.
• Stratum V
• All patients with verified diagnosis of LCH and MRI findings consistent with
ND-CNSLCH irrespective of previous treatments (also those not registered to other
Strata ofLCH-IV).
• Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion
in the hypothalamus-pituitary axis). In patients with already established
diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a
biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion
is needed for inclusion into the study
• Stratum VI
-- Patients with newly diagnosed SS-LCH and localization other than "multifocal
bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.
• Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as
consent for longterm follow-up has not been withheld.
Exclusion Criteria:
• Stratum I
• Pregnancy (patients of child-bearing age must be appropriately tested before
chemotherapy)
• LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis,
lung fibrosis, etc.) in the absence of active disease
• Prior systemic therapy
• Stratum II
• Patients with progressive disease in risk organs
• Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without
evidence of active LCH in the same organ or in any other locations
• No written consent of the patient or his/her parents or legal guardian
• Stratum III
• The presence of any of the following criteria will exclude the patient from the
study:
• Isolated sclerosing cholangitis without evidence of active hepatic LCH as the
only evidence of risk organ involvement.
• Inadequate renal function as defined by serum creatinine > 3x normal for age
• Stratum IV
• Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
• Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
• Uncontrolled active life-threatening infection.
• Decreased renal function with a GFR of less than 50ml/1.73m2/min.
• Pregnancy or active breast feeding
• Failure to provide signed informed consent
• Stratum VI
• Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible
for Stratum V),
• Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible
for Stratum I, Group 2)
Langerhans Cell Histiocytosis, Liver, Lung, Bones and Joints, Other Skin, Brain and Nervous System, Other Endocrine System, Other Hematopoietic, Brain/Central Nervous System, Endocrine cancers, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma
Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors
This clinical trial studies cancer survivors to identify those who are at increased risk of
developing late-occurring complications after undergoing treatment for childhood cancer. A
patient's genes may affect the risk of developing complications, such as congestive heart
failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer
treatment. Genetic studies may help doctors identify survivors of childhood cancer who are
more likely to develop late complications.
Kenneth Desantes, M.D.
All
up to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00082745
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Inclusion Criteria:
• ELIGIBILITY CRITERIA •CASES
• Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• Development of one of the following key adverse events at any time following
initiation of cancer therapy:
• Cardiac dysfunction; please note: case enrollment has been closed due to
achievement of target accrual
• Ischemic stroke (IS)
• Subsequent malignant neoplasm (SMN)
• Avascular necrosis (AVN); please note: case enrollment has been closed due to
achievement of target accrual
• Submission of a blood specimen (or in certain cases a saliva specimen) to the
Coordinating Center at the University of Alabama at Birmingham as per the
requirements; please note: if a patient is currently receiving active cancer
treatment, it is preferable to obtain the blood sample at a time when the patient's
white blood cell (WBC) is > 2,000
• Written informed consent from the patient and/or the patient's legally authorized
guardian
• In active follow up by a COG institution; active follow up will be defined as date of
last visit or contact by a COG institution within the past 24 months; any type of
contact, including contact specifically for participation in ALTE03N1, qualifies as
active follow-up; please note: treatment on a COG (or legacy group) therapeutic
protocol for the primary cancer is NOT required
• ELIGIBILITY CRITERIA •CONTROLS
• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell
transplant
• CONTROLS: No clinical evidence of any of the following key adverse events:
• Cardiac dysfunction (CD); please note: if a patient is currently receiving active
cancer treatment, it is preferable to obtain the blood sample at a time when the
patient's WBC is > 2,000
• Ischemic stroke (IS)
• Avascular necrosis (AVN)
• Subsequent malignant neoplasm (SMN)
• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to
the Coordinating Center Laboratory at the University of Alabama at Birmingham as per
the requirements
• CONTROLS: Written informed consent from the patient and/or the patient's legally
authorized guardian
• CONTROLS: In active follow up by a COG institution; active follow up will be defined
as date of last visit or contact by a COG institution within the past 24 months; any
type of contact, including contact specifically for participation in ALTE03N1,
qualifies as active follow-up; please note: treatment on a COG (or legacy group)
therapeutic protocol for the primary cancer is NOT required
Childhood Malignant Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia, not otherwise specified, Other Hematopoietic, Ill-Defined Sites, Other
Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM5)
B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with
multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC)
containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized,
open-label, platform study designed to evaluate the effects of belantamab mafodotin in
combination with other anti-cancer drugs in participants with relapsed/refractory multiple
myeloma. The Platform design incorporates a single master protocol, where multiple treatment
combinations, as sub-studies, will be evaluated simultaneously.
Natalie Callander, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04126200
Show full eligibility criteria
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Inclusion Criteria:
• Participant must be 18 years of age inclusive or older, at the time of signing the
informed consent.
• Participants must have histologically or cytologically confirmed diagnosis of Multiple
Myeloma (MM), as defined by the IMWG.
• Participants having at least 3 prior lines of prior anti-myeloma treatments including
an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38
monoclonal antibody.
• Participants with a history of autologous stem cell transplant are eligible for study
participation when, transplant was >100 days prior to study enrolment and with no
active infection(s).
• Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1,
unless ECOG less than equal to (<=)2 is due solely to skeletal complications and/or
skeletal pain due to MM.
• Participants with measurable disease defined as at least one of the following: Serum
M-protein greater than equal to (>=)0.5 gram per deciliter (>=5 gram per liter) or
Urine M-protein >=200 milligrams (mg) per 24 hours or Serum free light chain (FLC)
assay: Involved FLC level >=10 mg per deciliter (>=100 mg per Liter) and an abnormal
serum FLC ratio (<0.26 or >1.65).
• Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be
enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B
surface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable during
screening.
• Participants who are currently receiving physiological doses oral steroids (<10
mg/day), inhaled steroids or ophthalmalogical steroids.
Inclusion Criteria Specific to Sub-study 6,7, and 8:
• Participants with contraception requirements specific to Sub-study 6, 7, and 8
respectively.
• Participants with platelets value for Adequate Organ System Function is ≥75 × 10^9/L.
Inclusion Criteria Specific to Sub-study 8:
•In Japan, participants should reside in Japan and be Japanese as defined by having all
biological Japanese grandparents. Similarly, in China, subjects should reside in China and
be Chinese as defined by having all biological Chinese grandparents.
Exclusion Criteria:
• Participants with current corneal epithelial disease except mild punctate keratopathy.
• Participants with evidence of cardiovascular risk.
• Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy
to drugs chemically related to belantamab mafodotin or any of the components of the
study treatment. History of severe hypersensitivity to other mAb.
• Participants with active infection requiring antibiotic, antiviral, or antifungal
treatment.
• Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma
therapy within <14 days.
• Participants with prior radiotherapy within 2 weeks of start of study therapy.
• Participants with prior allogeneic transplant are prohibited.
• Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy
with lymphodepletion with chemotherapy within 3 months of screening.
• Participants with any major surgery (other than bone-stabilizing surgery) within the
last 30 days.
• Participants with prior treatment with an investigational agent within 14 days or 5
half-lives of receiving the first dose of study drugs, whichever is shorter.
• Participants with >=grade 3 toxicity considered related to prior check-point
inhibitors and that led to treatment discontinuation.
• Participants who have received transfusion of blood products within 2 weeks before the
first dose of study drug.
• Participants must not receive live attenuated vaccines within 30 days prior to first
dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in
any sub-study arm of the platform trial and for at least 70 days following last study
treatment.
• Participants with presence of active renal condition (infection, requirement for
dialysis or any other condition that could affect participant's safety). Participants
with isolated proteinuria resulting from MM.
• Participants with known human immunodeficiency virus (HIV) infection, unless the
participant can meet all criteria: a) established anti-retroviral therapy for at least
4 weeks and HIV viral load<400 copies/milliliter (mL) b) cluster of differentiation 4
plus (CD4+) T-cell (CD4+) counts >= 350 cells/microliter (µL) c) No history of
Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the
last 12 months in which case the participant would be eligible for CE Phase only.
For participants receiving nirogacestat, HIV drugs that are strong Cytochrome P450 3A4
(CYP3A4) inhibitors are prohibited. HIV drugs that are moderate CYP3A4 inhibitors, while
permitted, should be co-administered with caution and must be accompanied by nirogacestat
dose modifications.
Additional Exclusion Criteria for Sub-study 1 and 2:
• Participants with autoimmune disease (current or history) or syndrome that required
systemic treatment within the past 2 years.
• Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.
Additional Exclusion Criteria for Sub-study 3, 6, 7, and 8:
• Participants with uncontrolled small and/or large intestinal disease.
• Participants with uncontrolled skin disease.
• Participants with any condition causing hypophosphatemia, hypokalemia or
hypomagnesemia which is refractory to electrolyte replacement.
• Participants with previous administration of a gamma secretase inhibitor.
• Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.
Additional Exclusion Criteria for Sub-study 4:
• Participant has an active autoimmune disease that has required systemic treatment in
the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs).
• Participants who have received prior therapy with an anti-programmed death-1
(anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2)
agent.
• Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of study treatment. Use of inhaled steroids, local injection of steroids,
and steroid eye drops are allowed.
Additional Exclusion Criteria for Sub-study 5:
• Participants with Severe hypersensitivity to Isatuximab-irfc or to any of its
excipients.
• Participants with prior treatment with other anti-CD38 monoclonal antibody within 6
months of the first dose of study drug treatment.
• Participants with known intolerance or hypersensitivity to infused proteins products,
sucrose, histidine, and polysorbate 80.
Additional Exclusion Criteria for Sub-study 6, 7, and 8:
• Participants with active or history of venous thromboembolism within the past 3
months.
• Participants with evidence of active mucosal or internal bleeding.
• Participants with contraindications to or are unwilling to undergo protocol-required
anti-thrombotic prophylaxis or unable to tolerate antithrombolitic prophalaxis.
Additional Exclusion Criteria for Sub-study 6 and 8:
•Participants who discontinued prior treatment with lenalidomide due to intolerable
adverse events.
Additional Exclusion Criteria for Sub-study 7:
•Participants who discontinued prior treatment with pomalidomide due to intolerable
adverse events.
Additional Exclusion Criteria for Sub-study 8:
• Pregnant or lactating female or female who are interrupting lactation.
• Previously diagnosed with interstitial lung disease or current complication of
interstitial lung disease.
Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia (CLOVER-WaM)
Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell
malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small
lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia
(WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma
(DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with
standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy
study evaluating IV administration of iopofosine I 131 in patients with WM that have received
at least two prior lines of therapy.
Natalie Callander, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT02952508
Show full eligibility criteria
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[CLOVER-1]
Inclusion Criteria:
All Patients
• Histologically or cytologically confirmed MM; Patients with primary or secondary CNSL
may be enrolled.
• ECOG performance status of 0 to 2
• 18 years of age or older
• Life expectancy of at least 6 months
• Platelets ≥ 75,000/µL (if full-dose anticoagulation therapy is used, platelets ≥
100,000/µL are required)
• WBC count ≥ 3000/µL
• Absolute neutrophil count ≥ 1500/µL
• Hemoglobin ≥ 9 g/dL (last transfusion, if any, must be at least 1 week prior to study
registration, and no transfusions are allowed between registration and dosing)
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × upper
limit of normal (ULN)
• Bilirubin < 1.5 × ULN
• International normalized ratio (INR) < 2.5
• If patient is on full-dose anticoagulation therapy, the anticoagulation therapy must
be reversible and reversal of the anticoagulation therapy must not be
life-threatening, as judged by the Investigator
• Patients who have undergone stem cell transplant must be at least 100 days from
transplant
Patients with Multiple Myeloma
• At least 5 prior regimens, which must include at least 1 approved proteasome inhibitor
(bortezomib, carfilzomib, or ixazomib), at least 1 approved immunomodulatory agent
(thalidomide, lenalidomide, or pomalidomide), and at least 1 approved monoclonal
antibody (e.g., daratumumab or elotuzumab) with or without maintenance therapy, unless
patients are intolerable to such agents or ineligible to receive such agents.
• At least triple-class refractory (refractory to a proteasome inhibitor,
immunomodulatory agent, and a monoclonal antibody)
• Progressive disease defined by any of the following:
• 25% increase in serum M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in serum M-protein of ≥ 0.5 g/dL
• 25% increase in urine M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in urine M-protein of ≥ 200 mg/24 h
• 25% increase in bone marrow plasma cell percentage from the lowest response value
during (or after) last therapy. Absolute bone marrow plasma cell percentage must
be ≥ 10% unless prior CR when absolute bone marrow plasma cell percentage must be
≥ 5%.
• 25% increase in serum FLC level from the lowest response value during (or after)
last therapy; the absolute increase must be > 10 mg/dL
• New onset hypercalcemia > 11.5 mg/dL
• Failure to obtain a partial response or better to current treatment, or cannot
further improve their response to current treatment
• Appearance of new extramedullary disease
• Measurable disease defined by any of the following:
• Serum M-protein > 0.5 g/dL
• Urine M-protein > 200 mg/24 h
• Serum FLC assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is
abnormal.
[CLOSED] Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma,
Lymphoplasmacytic Lymphoma/Waldenstom Macroglobulinemia, or Marginal Zone Lymphoma
• Prior treatment with at least 2 prior regimens, which may include chemotherapy, an
approved anti-CD20 antibody with or without maintenance therapy, and an approved
targeted agent, unless patients are ineligible to receive such agents
• Patients with Helicobacter pylori+ mucosa-associated lymphoid tissue lymphoma must
have received 1 prior antibiotic regimen for H pylori
• At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Additional
parameters (e.g., measurable IgM for patients with Lymphoplasmacytic Lymphoma) may be
allowed if they meet current NCCN guidelines for symptomatic disease. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.
[CLOSED] Patients with Mantle Cell Lymphoma
• Prior treatment with at least 1 prior regimen
• At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.
[CLOSED] Patients with Diffuse Large B-Cell Lymphoma
• Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab
and an anthracycline; or is intolerable to such agents. Relapsed disease is defined as
either recurrence of disease after a CR or PD after achieving a partial response (PR)
or SD. Refractory disease is defined as failure to achieve at least SD with any 1 line
of therapy or with PD ≤ 3 months of the most recent chemotherapy regimen.
• At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.
Patients with CNS Lymphoma
• Must have biopsy-proven disease and must have received at least one prior intervention
for their disease.
• Must be at least two weeks from CNS biopsy before administration of iopofosine I 131.
• Must have at least one lesion with enhancement on brain imaging.
• Stable (or decreasing) dose of corticosteroids or anti-convulsant medication for at
least 7 days prior to dosing
[CLOVER-1]
Exclusion Criteria:
• Ongoing Grade 2 or greater toxicities due to previous therapies. Stable, tolerable
Grade 2 AEs (eg, neuropathy) may be allowed.
• Prior external-beam RT resulting in greater than 20% of total bone marrow receiving
greater than 20 Gy.
• Prior total body or hemi-body irradiation. Patients who have received prior low-dose
total body or hemi-body irradiation may be allowed on a case-by-case basis after
discussion with Sponsor (considerations may include factors such as time since
irradiation, total lifetime accumulated dose, etc.)
• Extradural tumor in contact with the spinal cord or tumor located where swelling in
response to therapy may impinge upon the spinal cord
• For patients with CLL/SLL, LPL, or MZL, transformation to a more aggressive form of
NHL
• Ongoing chronic immunosuppressive therapy
• Clinically significant bleeding event within prior 6 months
• Ongoing anti-platelet therapy (except low-dose aspirin [eg, 81 mg daily] for
cardioprotection)
• Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion. Low dose
dexamethasone for symptom management is allowed
• Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2
weeks of eligibility-defining bone marrow biopsy.
• For patients with primary or secondary CNSL, active bleeding in the tumor bed and/or
uncontrolled seizure activity
[CLOVER-WaM] Inclusion Criteria
• Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be
enrolled with prior Sponsor approval.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0
to 2 (Appendix C)
• Patient is 18 years of age or older
• Life expectancy of at least 6 months
• Received at least two prior lines of therapy for WM
• Measurable IgM (above upper limit of normal) OR at least one measurable nodal lesion
with longest diameter > 15 mm or one measurable extranodal lesion (e.g., hepatic
nodule) with longest diameter > 10 mm
[CLOVER-WaM] Exclusion Criteria
• Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia.
• Prior external-beam RT resulting in greater than 20% of total bone marrow receiving
greater than 20 Gy.
• Prior total body or hemi-body irradiation. Patients who have received prior low-dose
total body or hemi-body irradiation may be allowed on a case-by-case basis after
discussion with Sponsor (considerations may include factors such as time since
irradiation, total lifetime accumulated dose, etc.)
• Patients with second malignancies in addition to WM, if the second malignancy has
required therapy in the last 2 years or is not in remission; exceptions to this
criterion include successfully treated non-metastatic basal cell or squamous cell skin
carcinoma, or prostate cancer that does not require therapy
• Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion.
• Need for acute treatment of WM (e.g., those with hyperviscosity)
Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, Lymphoma, Waldenstrom Macroglobulinemia, Multiple Myeloma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Central Nervous System Lymphoma
S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration (DRAMMATIC)
Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step
2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2
(first randomization). Patients are randomized between Lenalidomide for 2 years and
Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide
further therapy. MRD-positive patients will continue with the assigned treatment.
MRD-negative patients will be further randomized (Reg Step 3) to either continue or
discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg
and followed for up to 15 years.
Natalie Callander, MD
All
18 Years to 75 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04071457
Show full eligibility criteria
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Registration Step 1 Except where otherwise indicated below that test is required in a
shorter timeframe, all tests for establishing baseline disease status must be completed
within 60 days prior to registration. All test results must be documented on the Baseline
Tumor Assessment Form for Multiple Myeloma and the Onstudy Form.
Inclusion Criteria
• Patients must have had a confirmed diagnosis of symptomatic multiple myeloma (See
Section 4.1) that required systemic induction therapy prior to autologous stem cell
transplantation (ASCT).
• Patients with disease measurable by serum light chain assay alone are eligible
(defined as >/= 100 mg/L on involved light chain).
• Patients must be registered to Step 1 prior to registration to Step 2. Registration to
Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but
after completion of induction therapy.
• Patients must have initiated induction therapy within 12 months prior to registration
Step 1 and have received at least two cycles of induction therapy.
• Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular
weight heparin, warfarin, or equivalent oral anticoagulation).
• Patients must be >/= 18 and = 75 years of age at time of registration to Step 1.
• Patients must have history and physical exam within 28 days prior to registration.
• Patients must have Zubrod Performance Status = 2.
• Patients must have evidence of adequate renal function, as defined by (1) creatinine
clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or
estimated by the Cockcroft and Gault formula, or (2) serum creatinine < 2.5 mg/dL.
Values must be obtained within 28 days prior to registration.
• Patients must have adequate hepatic function defined by the following within 42 days
prior to registration:
• Total bilirubin =1.5 x IULN (institutional upper limit of the norm) AND
• AST and ALT =3.0 x IULN
• Patients must meet one of the following criteria:
• Be acceptable for transplant per institutional guidelines and the criteria
evidencing this must be documented on the S1803 Onstudy Form. (See Appendix 18.3
for standard transplant eligibility guidelines. Note that these are guidelines
and not required criteria.) OR
• Have completed autologous stem cell transplant within 180 days prior to
registration (see also Section 5.2a).
• Patient's with human immunodeficiency virus (HIV) are eligible providing they are on
effective antiretroviral therapy and have undetectable viral load at their most
previous viral load test and within 6 months prior to registration.
• Patients must be able to take and swallow oral medication (capsules) whole. Patients
may not have any known impairment of gastrointestinal function or gastrointestinal
disease that may significantly alter the absorption of study drug (e.g. ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).
• For patients who have not yet received transplant: Patients must be willing and able
to return to the transplant center for their assigned treatment after randomization.
Note that patients need not have a direct relationship with the transplant center in
order to register.
• Patients must submit specimens for MRD as outlined in Section 15.1. See Section 15.1
for further information, including specimen submission timepoints. Note that patients
are not ineligible based solely on archival specimens being unavailable.
• Patients must be offered participation in specimen banking for future research. With
patient's consent, specimens must be submitted as outlined in Section 15.2.
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines.
• As a part of the OPEN registration process (see Section 13.3 for OPEN access
instructions) the treating institution's identity is provided in order to ensure that
the current (within 365 days) date of institutional review board approval for this
study has been entered in the system.
Exclusion Criteria
• Patients with smoldering myeloma are not eligible. Patients with purely non-secretory
MM as measured by electrophoresis and immunofixation and the absence of Bence Jones
proteins in the urine are not eligible. Patients must have measurable M protein in the
serum (defined as >/= 0.5g/dL) or urine (defined as >/= 200 mg/24h). Patients with
plasma cell leukemia are not eligible.
• Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis
related organ dysfunction.
• Patients must not have progressive disease at any time prior to registration.
• Patients must not be refractory to either lenalidomide or daratumumab/rHuPH20.
• Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH20.
• Patients must not have received any investigational agents within 14 days prior to
registration.
• Patients must not have chronic obstructive pulmonary disease with a forced expiratory
volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for patients
suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1
is < 50% of predicted normal.
• Patients must not have moderate or severe persistent asthma within the past 2 years
and must not have currently uncontrolled asthma of any classification.
• Patients must not have had prior autograft or allograft, or prior organ transplant
requiring immunosuppressive therapy.
• Patients must not have known allergy to any of the study drugs.
• Patients with uncontrolled bacterial, viral or fungal infections (currently taking
medication and with progression or no clinical improvement) at time of enrollment are
not eligible.
• Patients must not have known central nervous system (CNS) involvement with multiple
myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS
plasmacytoma at time of enrollment. Lumbar puncture is not required.
• Patients must not be seropositive for hepatitis C (except in the setting of sustained
virologic response, defined as undetectable viral load at least 12 weeks after
completion of antiviral therapy). HCV testing is only required if clinically indicated
or if the patient has a history of HCV.
• No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or any
other cancer from which the patient has been disease free for three years.
• Patients must not have any uncontrolled intercurrent illness including (not limited
to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty,
or stenting within 6 months prior to registration, Unstable cardiac arrhythmia
(ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade >/= 2), intra-cardiac
defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>/=
Grade 3), or known psychiatric illness that would limit study compliance.
Registration Step 2 •First Randomization (Post-ASCT, Pre-Maintenance)
Inclusion Criteria:
• Patients must have completed ASCT within 180 days prior to registering to Step 2.
• Patients must have one of the following performed within 60 days prior to registration
for disease assessment: diagnostic quality skeletal survey, whole body CT scan, MRI,
or PET.
• Patients must have Zubrod Performance Status = 2
• Patients must have adequate bone marrow function as evidenced by platelets >/=
75,000/mm3 and ANC >/= 1,000/mm3 within 28 days prior to first randomization:
• Patients must have adequate hepatic function defined by the following within 28 days
prior to first randomization:
• Total bilirubin =1.5 x IULN (institutional upper limit of the norm) AND AST and ALT
=3.0 x IULN
• Patients must have evidence of adequate renal function, as defined by creatinine
clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or
estimated by the Cockcroft and Gault formula, or have a serum creatinine < 2.5 mg/dL
within 28 days prior to first randomization.
• All ASCT-related toxicities must have recovered to =Grade 1 (except for alopecia,
fatigue and amenorrhea) prior to first randomization.
• Mucositis and gastrointestinal symptoms must have resolved to =Grade 1.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration.
• FCBP must agree to have a second pregnancy test within 24 hours prior to starting
Cycle 1. Further, FCBP must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control: one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
starting lenalidomide. FCBP must also agree to ongoing pregnancy testing and must
agree to not become pregnant for at least 3 months after the last dose of study
treatment.
• Men must agree to use a latex condom during sexual contact with a FCBP, even if they
have had a successful vasectomy, during the study treatment and for 3 months after the
last dose of study treatment.
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines.
Exclusion Criteria:
• Patients must not have received any other maintenance therapy post-ASCT and prior to
Step 2 registration.
• Patients must not have had progressive disease between induction and registration to
Registration Step 2. (See Section 10.1b).
Registration Step 3 •Second Randomization (Post 24 Months Maintenance)
Inclusion Criteria:
• Patients must have completed 24 cycles of protocol maintenance with either
lenalidomide or lenalidomide + daratumumab/rHuPH20.
• Patients must have 24-month MRD by NGS test results available and must be MRD
negative. Patients whose PCR results are indeterminable will be considered to have
positive results.
• Patients must be in very good partial remission (VGPR) or better by IMWG response
criteria (see Section 10.1b).
Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma
This phase III trial studies how well lenalidomide and dexamethasone works with or without
daratumumab in treating patients with high-risk smoldering myeloma. Drugs used in
chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the
growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab,
may induce changes in the body's immune system and may interfere with the ability of tumor
cells to grow and spread. Giving lenalidomide and dexamethasone with daratumumab may work
better in treating patients with smoldering myeloma.
Natalie Callander, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03937635
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma
(SMM) within the past 12 months. High-risk is defined by the presence of 2 or more of
the following factors:
• Abnormal serum free light chain ratio of involved to uninvolved >20, but less
than 100 if the involved FLC is >= 10 mg/dL by serum free light chain (FLC) assay
• Serum M-protein level >= 2 gm/dL
• Presence of t(4;14) or del 17p, del 13q or 1q gain by conventional cytogenetics
or fluorescence in situ hybridization (FISH) studies.
• >20% plasma cells on biopsy or aspirate
• Bone marrow aspirate and/or biopsy is required to be performed within 42 days prior to
randomization and must demonstrate 10-59% clonal plasma cells.
• >= 1 g/dL on serum protein electrophoresis (within 28 days prior to randomization).
• >= 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis (within 28
days prior to randomization).
• NOTE: In the rare situation where the serum protein electrophoresis (SPEP) is
felt to be unreliable, then quantitative immunoglobulin levels on nephelometry or
turbidometry can be accepted.
• SPEP, urine protein electrophoresis (UPEP), and serum FLC are required to be performed
within 28 days prior to randomization.
• NOTE: UPEP (on a 24-hour collection) is required; no substitute method is
acceptable. Urine must be followed monthly if the baseline urine M-spike is >=
200 mg/24 hour (hr), and urine in addition to serum must be followed in order to
confirm a very good partial response (VGPR) or higher response.
• Patients must have no lytic lesions, no known plasmacytoma, and no unexplained
hypercalcemia (i.e., > 11 mg/dL or 1mg/dL above upper limit of normal [ULN]).
• Hemoglobin >= 11 g/dL (within 28 days prior to randomization).
• Platelet count >= 100,000 cells/mm^3 (within 28 days prior to randomization).
• Absolute neutrophil count >= 1500 cells/mm^3 (within 28 days prior to randomization).
• Calculated creatinine clearance >= 30 mL/min (within 28 days prior to randomization).
• Bilirubin =< 1.5 mg/dL (within 28 days prior to randomization).
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and
serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
2.5 times the upper limit of normal (within 28 days prior to randomization).
• Patients must not have any prior or concurrent systemic or radiation therapy for the
treatment of myeloma. Patients must also not have contraindication to deep vein
thrombosis (DVT) prophylaxis/aspirin.
• Patients must not have more than one focal marrow lesion on magnetic resonance imaging
(MRI) of either pelvis or spine. Patients with indwelling pacemakers and/or ICD
(implantable cardioverter-defibrillator) that is known or suspected to be MRI
incompatible will be excused from this test.
• Concurrent use of erythropoietin is not allowed while on study therapy.
• Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not
permitted. Prior systemic glucocorticosteroid use for the treatment of non-malignant
disorders is permitted; concurrent use after registration on the study should be
restricted to the equivalent of prednisone 10 mg per day. Prior or concurrent topical
or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is
permitted.
• Patients must not have active, uncontrolled seizure disorder. Patients must not have
had a seizure in the last 6 months.
• Patients must not have uncontrolled intercurrent illness including uncontrolled
hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled
cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would
limit compliance with the study, or a prior history of Stevens Johnson syndrome.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0,
1, or 2.
• Patients with monoclonal gammopathy of undetermined significance are not eligible.
• Patients must not have grade 2 or higher peripheral neuropathy per CTCAE.
• Patients must not have active, uncontrolled infection.
• Patients may have a history of current or previous deep vein thrombosis or pulmonary
embolism but are required to take some form of anti-coagulation as prophylaxis if they
are not currently on full-dose anticoagulation.
• Patients should not have New York Heart Association classification III or IV heart
failure at baseline.
• Patients with a history of prior malignancy are eligible provided they were treated
with curative intent and have been free of disease for the time period considered
appropriate for cure of the specific cancer. For most diseases this time frame is 5
years.
• Patients must agree to register into the mandatory Risk Evaluation and Mitigation
Strategy (REMS) program and be willing and able to comply with the requirements of
REMS.
• Women must not be pregnant due to potential harm to the fetus from daratumumab and
lenalidomide. All females of childbearing potential (FCBP) must have a blood test or
urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the
first dose of lenalidomide and again within 24 hours prior to the first dose of
lenalidomide. FCBP must also agree to ongoing pregnancy testing while on treatment. A
female of childbearing potential is any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria: 1) has
achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months
(i.e., has had menses at any time in the preceding 24 consecutive months).
• Females of childbearing potential (FCBP) must either abstain from sexual intercourse
for the duration of their participation in the study or agree to use TWO acceptable
methods of birth control, one highly effective method and one additional effective
method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2)
while participating in the study; 3) during dose interruptions; and 4) for at least 28
days after the last dose of protocol treatment (FCBP who are assigned to Arm A and
receive daratumumab must extend this contraception requirement to 3 months after the
last dose of protocol treatment). Women must also agree to not breastfeed during this
same time period. Men must agree to either abstain from sexual intercourse for the
duration of their participation in the study or use a latex condom during sexual
contact with a FCBP while participating in the study and for 28 days after the last
dose of protocol treatment even if they have had a successful vasectomy. Men must also
agree to abstain from donating sperm while on study treatment and for 28 days after
the last dose of protocol treatment even if they have had a successful vasectomy. Both
women and men must both agree to abstain from donating blood during study
participation and for at least 28 days after the last dose of protocol treatment.
• Human immunodeficiency virus (HIV)+ patients with undetectable HIV viral loads tested
within 6 months are eligible.
• Patients should not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to daratumumab, lenalidomide, or
dexamethasone.
• Patients must not have known chronic obstructive pulmonary disease (COPD) with a
forced expiratory volume in 1 second (FEV1) <50% of predicted normal or known moderate
or severe persistent asthma within 2 years prior to randomization
Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission
This randomized phase III trial studies rituximab after stem cell transplant and to see how
well it works compared with rituximab alone in treating patients with in minimal residual
disease-negative mantle cell lymphoma in first complete remission. Monoclonal antibodies,
such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving
chemotherapy before a stem cell transplant helps kill any cancer cells that are in the body
and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to
grow. After treatment, stem cells are collected from the patient's blood and stored. More
chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem
cells are then returned to the patient to replace the blood-forming cells that were destroyed
by the chemotherapy. Giving rituximab with or without stem cell transplant may work better in
treating patients with mantle cell lymphoma.
Vaishalee Kenkre, MD
All
18 Years to 70 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03267433
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Inclusion Criteria:
• INCLUSION CRITERIA FOR SCREENING (STEP 0 •PREREGISTRATION)
• Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by
immunohistochemical stains and/or t(11;14) by cytogenetics or FISH. If patient has
cyclin D1 negative mantle cell lymphoma with classical morphology and an expression
profile (including SOX11+) that is otherwise indistinguishable from mantle cell
lymphoma, communication with investigator is required for consideration of enrollment.
The proliferation rate, using Ki-67 or MIB-1, should also be determined, but is not
required until Step 1 registration. Patients may register to Step 0 without a
documented Ki-67 index.
• Patients should be deemed to be potentially eligible and willing candidates for
auto-HCT by the enrolling physician
• Patient may be receiving or have completed induction therapy within 60 days prior to
preregistration to step 0; no more than 300 days may have passed between the first day
of induction therapy and preregistration to step 0
• For patients who have completed induction therapy, restaging evaluation must show
status of partial (PR) or complete response (CR); patients preregistered
post-induction with evidence of clinical disease progression are not eligible for
preregistration
• Up to two regimens of chemotherapy are allowed as long as a continuous response
was ongoing throughout therapy
• NOTE: For example, a patient who started treatment with
rituximab/bendamustine and was then switched to
rituximab(R)-cyclophosphamide, doxorubicin hydrochloride, vincristine
sulfate, and prednisone (CHOP) (due to insufficient response or excessive
toxicity) would be counted as having received 2 regimens; however, R-CHOP
alternating with R-dexamethasone, high-dose cytarabine, and cisplatin (DHAP)
as a planned induction regimen would count as one regimen
• Patient does not have any documented history of central nervous system (CNS)
involvement by mantle cell lymphoma; this includes no evidence of parenchymal brain,
spinal cord, or cerebrospinal fluid involvement; radiculopathy symptoms from nerve
root compression by lymphoma do not constitute CNS involvement
• Patient must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue
specimen from the original diagnostic biopsy available for submission to Adaptive
Biotechnologies for ClonoSEQ ID molecular marker identification of unique clonal
immunoglobulin deoxyribonucleic acid (DNA) sequence
• NOTE: Patients for whom the molecular marker is identified will have peripheral
blood collected after completion of induction (patient?s disease status is PR or
CR) and submitted to Adaptive Biotechnologies for minimal residual disease (MRD)
assessment
• INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1)
• Patients must have met eligibility criteria for the screening step
• Institution has received results from Adaptive Biotechnologies as defined by one of
the following criteria:
• Patients are ?MRD Indeterminate?: ClonoSEQ ID molecular marker assessment did not
identify any unique clonal immunoglobulin DNA sequence OR
• ClonoSEQ ID molecular marker assessment identified unique clonal immunoglobulin
DNA sequence and MRD assessment is completed
• Patients must have completed induction therapy within 120 days prior to
preregistration to step 0, AND no more than 300 days may have elapsed from the first
dose of induction chemotherapy (cycle 1 [C1] day 1 [D1]) given, until the last day of
induction chemotherapy administered; for those assigned to Arms A, C, or D, the date
of transplant (?day 0?) must not be greater than 365 days after the first dose of
induction chemotherapy (C1D1) given
• Patient must have received at least four (4) cycles of induction therapy
• Up to two regimens of chemotherapy are allowed as long as a continuous response
was ongoing throughout therapy
• NOTE: For example, a patient who started treatment with
rituximab/bendamustine and was then switched to R-CHOP (due to insufficient
response or excessive toxicity) would be counted as having received 2
regimens; however, R-CHOP alternating with R-DHAP as a planned induction
regimen would count as one regimen
• Patients must have achieved a radiologic complete or partial remission as defined by
the Lugano criteria
• Patients must meet institutional eligibility requirements for stem cell transplant,
including cardiac, renal, liver, and pulmonary requirements
• Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Human immunodeficiency virus (HIV) positive patients are not excluded, but to enroll,
must meet all of the below criteria:
• HIV is sensitive to antiretroviral therapy
• Must be willing to take effective antiretroviral therapy if indicated
• CD4 count at screening >= 300 cells/mm^3
• No history of acquired immune deficiency syndrome (AIDS)-defining conditions
• Patient must be disease-free >= 3 years of prior malignancies with the exception of
adequately treated non-melanoma skin cancer, adequately treated in situ carcinoma, low
grade prostate carcinoma (Gleason grade =< 6) managed with observation that has been
stable for at least 6 months
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood test or urine study
within 2 weeks prior to registration to rule out pregnancy
• A female of childbearing potential is any woman, regardless of sexual orientation
or whether they have undergone tubal ligation, who meets the following criteria:
1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study
Study of Belantamab Mafodotin Plus Standard of Care (SoC) in Newly Diagnosed Multiple Myeloma (DREAMM 9)
This study will evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity
of belantamab mafodotin in combination with Velcade (bortezomib), Revlimid (lenalidomide),
dexamethasone (VRd) and will determine recommended phase 3 dose (RP3D) in adult participants
with newly diagnosed multiple myeloma (NDMM). Participants will receive the combination of
bortezomib, lenalidomide and dexamethasone (VRd) on a 3-week cycle until cycle 8, followed by
the combination of lenalidomide and dexamethasone (Rd) on a 4-week cycle thereafter as per
dosing schedule. Participants will receive belantamab mafodotin on a schedule that is
dependent on the cohort to which they are assigned. Belantamab mafodotin will be administered
in combination with VRd every 3 weeks (Q3W), every 6 weeks (Q6W), or every 9 weeks (Q9W) to
Cycle 8, and then in combination with Rd every 4 weeks (Q4W), every 8 weeks (Q8W), or every
12 weeks (Q12W) thereafter. Participants will complete an End of Treatment (EOT) visit at the
point of study treatment discontinuation, followed by a Safety Follow-up visit 70 days after
EOT.
Natalie Callander, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04091126
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Inclusion Criteria:
• Participant must be over 18 years of age inclusive, at the time of signing the
informed consent.
• Diagnosis of multiple myeloma with a requirement for treatment as documented per
international myeloma working group (IMWG) criteria.
• Must have at least one aspect of measurable disease, defined as one of the following:
• Urine M-protein excretion >=200 mg/24 hours (>=0.2 gram [g]/24 hours), or
• Serum M-protein concentration >=0.5 grams per deciliter (g/dL) (>=5.0 gram per liter
[g/L]), or
• Serum free light chain (FLC) assay: involved FLC level >=10 milligrams per deciliter
(mg/dL) (>=100 milligram per liter [mg/L]) and an abnormal serum free light chain
ratio (<0.26 or >1.65).
• Not a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT)
due to presence of significant comorbid condition(s), such as cardiac, pulmonary or
other major organ dysfunction that are likely to have a negative impact on
tolerability of high dose chemotherapy with stem cell transplantation, as judged by
the investigator.
• Eastern cooperative oncology group (ECOG) status of 0-2
• Adequate organ system functions as defined by the laboratory assessments listed as
following: Absolute neutrophil count (ANC) >=1.5 x 10^9/L; Hemoglobin >=8.0 g/dL;
Platelets >=75 x 10^9/L; Total bilirubin <=1.5 x upper limit of normal (ULN);
(Isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct
bilirubin is <35%); Alanine aminotransferase (ALT) <=2.5 x ULN; eGFR >=30
mL/minute/1.73 meter^2; Urine Dipstick for protein OR Albumin/creatinine ratio (from
spot urine)- Negative/trace (if >=1 plus only eligible if confirmed <=500 mg/gram (56
mg/millimoles [mmol]) by albumin/creatinine ratio (spot urine from first void); Left
Ventricular Ejection Fraction (LVEF) by echocardiogram (ECHO) of >=35% participants
with low LVEF (per institutional standards), consider referring to cardiology per
local standards of care.
• Sex and Contraception/Barrier Requirements (Female):
• Contraceptive use by women should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies. A female
participant is eligible to participate if she is not pregnant or breastfeeding, and at
least 1 of the following conditions applies:
• Is NOT a woman of childbearing potential (WOCBP) or Due to lenalidomide being a
thalidomide analogue with risk for embryofetal toxicity and prescribed under a
pregnancy prevention/controlled distribution program, and bortezomib having the
potential to cause fetal harm, WOCBP participants will be eligible if they commit to
either: abstain continuously from heterosexual sexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis) and agree to
remain abstinent OR to use birth control as follows: Two methods of reliable birth
control (one method that is highly effective and one additional effective (barrier)
method), beginning 4 weeks prior to initiating treatment with lenalidomide, during
therapy, during dose interruptions and continuing for 4 weeks following
discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use one
method of reliable birth control that is highly effective for a further 3 months
following discontinuation of belantamab mafodotin, or a further 6 months following
discontinuation of bortezomib, whichever is longer. WOCBP must also agree not to
donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during
dose interruptions and for 28-days following the last dose of lenalidomide, 4 months
following discontinuation of belantamab mafodotin treatment or 7-months following the
last dose of bortezomib, whichever is longer. Two negative pregnancy tests must be
obtained prior to initiating therapy. The first test should be performed within 10-14
days and the second test within 24 hours prior to prescribing the start of
lenalidomide therapy.
The participant should not receive lenalidomide until the investigator has verified that
the results of these pregnancy tests are negative. The investigator should evaluate the
effectiveness of the contraceptive method in relationship to the first dose of study
intervention. The Investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a woman with an
early undetected pregnancy.
• Sex and Contraception/Barrier Requirements (Male):
• Contraceptive use by men should be consistent with local regulations regarding the
methods of contraception for those participating in clinical studies
• Male participants are eligible to participate if they agree to the following from the
time of first dose of study treatment until 28-days after the last dose of
lenalidomide, 4-months after the last dose of bortezomib, or 6 months after the last
dose of belantamab mafodotin, whichever is longer, to allow for clearance of any
altered sperm: Refrain from donating sperm •Plus either: •Be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long
term and persistent basis) and agree to remain abstinent OR Must agree to use
contraception/barrier as detailed below: Agree to use a male condom, even if they have
undergone a successful vasectomy, and female partner to use an additional highly
effective contraceptive method with a failure rate of <1% per year when having sexual
intercourse with a WOCBP. Male participants should also use a condom when having
sexual intercourse with pregnant females.
• Capable of giving signed informed consent.
Exclusion Criteria:
• Smoldering multiple myeloma (SMM).
• Prior systemic therapy for multiple myeloma, or SMM. NOTE: An emergency course of
steroids (defined as no greater than 40 mg of dexamethasone, or equivalent per day for
a maximum of 4 days (that is, a total of 160 mg) is permitted. NOTE: Focal palliative
radiation is permitted prior to enrollment, provided that it occurred at least 2 weeks
prior to the first dose of study drug, that the participant has recovered from
radiation-related toxicities, and that the participant did not require corticosteroids
for radiation-induced adverse events.
• Participant is eligible for high dose chemotherapy with ASCT, as determined by a
frailty score of 0 as assessed by the IMWG frailty index.
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE)
Version 5.
• Major surgery within 4 weeks prior to the first dose of study drug.
• Presence of active renal condition (infection, requirement for dialysis or any other
significant condition that could affect participant's safety). Participants with
isolated proteinuria resulting from multiple myeloma (MM) are eligible, provided they
fulfil criteria.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other
conditions (including lab abnormalities) that could interfere with participant's
safety, obtaining informed consent or compliance to the study procedures.
• Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not
explained by reversible coagulopathy.
• Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic
gallstones, or otherwise stable chronic liver disease as per the Investigator's
assessment).
• Participants with previous or concurrent malignancies other than multiple myeloma are
excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other
malignancy that has been considered medically stable for at least 2 years. The
participant must not be receiving active therapy, other than hormonal therapy for this
disease. Note: Participants with curatively treated non-melanoma skin cancer are
allowed without a 2-year restriction.
• Evidence of cardiovascular risk including any of following: Evidence of current
clinically significant untreated arrhythmias, including clinically significant
electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or
third degree atrioventricular (AV) block; History of myocardial infarction, acute
coronary syndromes (including unstable angina), coronary angioplasty, or stenting or
bypass grafting within 3 months of Screening.; Class III or IV heart failure as
defined by the New York Heart Association (NYHA) functional classification system;
Uncontrolled hypertension.
• Active infection requiring treatment.
• Known human immunodeficiency virus (HIV) infection.
• Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb),
at Screening or within 3 months prior to first dose of study treatment.
• Positive hepatitis C antibody test result.
• Current corneal epithelial disease except for mild punctate keratopathy. Note:
Participants with mild punctate keratopathy are allowed.
• Intolerance or contraindications to anti-viral prophylaxis.
• Unable to tolerate antithrombotic prophylaxis.
• AL amyloidosis (light chain amyloidosis), active polyneuropathy, organomegaly,
endocrinopathy, monoclonal plasma proliferative disorder, skin changes (POEMS)
syndrome or active plasma cell leukemia at the time of screening.
• Exhibiting clinical signs of or has a known history of meningeal or central nervous
system involvement by multiple myeloma.
• Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
drugs chemically related to belantamab mafodotin, or any of the components of the
study treatment.
• Use of an investigational drug within 14 days or five half-lives (whichever is longer)
preceding the first dose of study drug.
• Plasmapheresis within 7 days prior to the first dose of study drug.
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric
patients with high-risk neuroblastoma.
Kenneth Desantes, M.D.
All
Not specified
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04023331
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Inclusion Criteria:
1. Participant is able and willing to provide informed consent (≥18 years), or informed
consent is obtained by the parent or legal guardian for minor participants, with the
minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has
relapsed or progressed to high-risk, with failure to achieve complete response with
standard therapy (defined as at least 4 cycles of aggressive multi-drug induction
chemotherapy with or without radiation and surgery, or according to a standard
high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to
receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the
Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within
28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet
count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+
cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective
method of birth control while participating on this study, to avoid possible damage to
the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than
that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
1. Participants with disease of any major organ system that would compromise their
ability to tolerate therapy, as deemed by the Investigator or treating
Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance,
oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or
radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the
administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney
within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of
64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior
to the administration of 64Cu-SARTATE), or short acting somatostatin analogues
(administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures
or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned
single or cumulative administered activity is modelled to deliver a radiation dose to
the marrow that exceeds 2 Gy.
Neuroblastoma, Relapsed Neuroblastoma, Refractory Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer
This phase I trial studies the side effects and best dose of peposertib when given together
with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low
grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving peposertib and pegylated
liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer
compared to pegylated liposomal doxorubicin hydrochloride alone.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04092270
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Inclusion Criteria:
• DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian,
fallopian tube or primary peritoneal cancer are eligible. This includes, but is not
limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/
high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not
otherwise specified
• NOTE: Patients who have evidence of DDR deficiency /HRD are eligible if they are
at the point in their disease course where they are appropriate candidates for
single agent Doxil
• EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low
grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)
• Patients accrued to the LGSOC cohort will have recurrent or persistent low grade
serous ovarian cancer or grade 1 serous ovarian cancer
• Patients accrued to the HGSOC cohort will have recurrent or persistent high grade
serous ovarian cancer
• Patients must have measurable disease by defined Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria
• Prior therapy:
• Patients must have received at least one prior line of platinum-based
chemotherapy
• Patients can have received an unlimited number of additional lines of
chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
• Any prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted therapy, immunotherapy, or hormonal therapy must be
discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest)
prior to study treatment initiation
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in
patients < 18 years of age, children are excluded from this study, but will be
eligible for future pediatric trials
• Patients with platinum-sensitive ovarian cancer are eligible for only the dose
expansion phase if their provider feels that PLD would be an appropriate treatment
option for them. Patients with platinum-sensitive ovarian cancer should also be
offered any higher priority studies for which they are potentially eligible and/or
platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients must have a cardiac ejection fraction >= the institutional lower limit of
normal (LLN)
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
• Alkaline phosphatase =< 2.5 x institutional ULN
• Creatinine clearance > 30 ml/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression. The
patient must be off steroids and clinically stable
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
• The effects of peposertib (M3814) and liposomal doxorubicin on the developing
human fetus are unknown and there is the potential for teratogenic or
abortifacient effects. For this reason, women and men of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study treatment,
and for 6 months after completion of peposertib (M3814) administration. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with peposertib (M3814),
breastfeeding should be discontinued if the mother is treated with peposertib
(M3814)
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
• Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36
months prior to registration must be available for submission for deoxyribonucleic
acid (DNA)/ribonucleic acid (RNA) analysis
Exclusion Criteria:
• Patients are excluded from the dose-escalation phase of the study if they are eligible
for any available therapies known to confer clinical benefit
• Inability to swallow and/or absorb oral medication (patients with a drainage peg are
ineligible)
• Patients may not have received prior anthracyclines (doxorubicin or pegylated
liposomal doxorubicin) for treatment of their ovarian cancer
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia, thyroid
dysfunction, or neuropathy
• Patients who are receiving any other investigational agents within 28 days prior to
start of treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to peposertib (M3814) or pegylated liposomal doxorubicin
• Patients who cannot discontinue concomitant medications or herbal supplements that
potentially interact with peposertib (M3814)
• The following categories of medications and herbal supplements must be
discontinued prior to starting study treatment:
• Strong inducers/inhibitors of CYP3A4/5, CYP2C9, and CYP2C19
• Substrates of CYP3A4/5, CYP1A2, and CYP2B6 with a narrow therapeutic index
• Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6 and substrates of
P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 with a narrow therapeutic index. Close
monitoring is advised
• Because the lists of these agents are constantly changing, it is important to
regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk
of interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or
herbal product. Patient Drug Interactions Handout and Wallet Card) should be
provided to patients
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients
may confer with the study doctor to determine if such medications can be discontinued.
These must be discontinued >= 5 days prior to study treatment. Patients do not need to
discontinue calcium carbonate
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
are excluded
• Patients who have received a live attenuated vaccine within 30 days of dosing with
peposertib (M3814)
• Patients with uncontrolled intercurrent illness, including but not limited to ongoing
or active infection
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because peposertib (M3814) is DNA-PK
inhibitor agent with the potential for teratogenic or abortifacient effects. Because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with peposertib (M3814), breastfeeding should be
discontinued if the mother is treated with peposertib (M3814). These potential risks
may also apply to other agents used in this study
• Patients with significant (uncontrolled) cardiac conduction abnormalities are excluded
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
This phase III trial compares the combination of four drugs (daratumumab, bortezomib,
lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab,
lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Daratumumab is a monoclonal antibody
that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory
drugs, such as dexamethasone lower the body's immune response and are used with other drugs
in the treatment of some types of cancer. Adding bortezomib to daratumumab, lenalidomide, and
dexamethasone may be more effective in shrinking the cancer or preventing it from returning,
compared to continuing on daratumumab, lenalidomide, and dexamethasone.
Timothy Schmidt, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04566328
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• STEP 0 •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance
status (PS) of 0-2 (PS 3 allowed if secondary to pain)
• STEP 0 •Patient must have newly diagnosed multiple myeloma (MM) by International
Myeloma Working Group (IMWG) criteria
• STEP 0 •Patient must agree to register to the mandatory REVLIMID Risk Evaluation and
Mitigation Strategy (RevREMS) program and be willing and able to comply with the
requirements of RevREMS
• STEP 0 •Patient must be able to undergo diagnostic bone marrow aspirate following
preregistration.
• NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies
for clonoSEQ Assay
• NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from
the Clonality (ID) test within fourteen (14) days of receipt and reconciliation
of fresh bone marrow specimen to the submitting institution
• STEP 1 •Patient must meet all eligibility criteria in STEP 0 with exception of
allergy requirement
• STEP 1 •Institution must have received the Clonality (ID) test results from Adaptive
Biotechnologies and dominant sequences were identified
• STEP 1 •Patient must have standard risk MM as defined by the Revised International
Staging System (RISS) stage I or II
• NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate
dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA)
detected by interphase fluorescent in situ hybridization (iFISH). Presence of
del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these,
including any other findings, are standard risk
• R-ISS stage
• Stage I: ISS stage I [beta2 macroglobulin < 3.5 mg/L, albumin > 3.5 g/dL]
AND standard-risk CA AND normal LDH
• Stage II: Not R-ISS stage I or III
• Stage III: ISS stage III [beta2 macroglobulin > 5.5 mg/L] AND high-risk CA
OR high LDH (> upper limit of normal) [patients with stage III are
ineligible]
• STEP 1 •Patient must have measurable or evaluable disease as defined by having one or
more of the following, obtained within 28 days prior to registration:
• >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
• >= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein
electrophoresis
• Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
• Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
• STEP 1 •Patients must have a serum protein electrophoresis (SPEP), urine protein
electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28
days prior to registration. In addition, a bone marrow biopsy and/or aspirate is
required within 28 days if bone marrow is being followed for response
• NOTE: UPEP (on a 24-hour collection) is required, no substitute method is
acceptable. Urine must be followed monthly if the baseline urine M-spike is >=
200 mg/24 hr. Please note that if both serum and urine M-components are present,
both must be followed in order to evaluate response
• NOTE: The serum free light chain test is required to be done if the patient does
not have measurable disease in the serum or urine. Measurable disease in the
serum is defined as having a serum M-spike >= 1 g/dL. Measurable disease in the
urine is defined as having a urine M-spike >= 200 mg/24 hr
• STEP 1 •Calculated creatinine clearance > 30 mL/min (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to Step
1 registration)
• STEP 1 •Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained
=< 14 days prior to Step 1 registration)
• STEP 1 •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
ULN (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Patient must have received no more than one cycle (28 days or less) of prior
chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed
to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to
symptomatic lesions is allowed provided there are no residual toxicity related to
radiation and blood counts meet the study requirements. Radiation treatment must be
completed at least 14 days prior to Step 1 registration
• STEP 1 •Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months of randomization
are eligible for this trial
• STEP 1 •For patients with evidence of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy, if indicated
• STEP 1 •Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
• STEP 1 •Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial
• STEP 1 •Patients with known history or current symptoms of cardiac disease, or
history of treatment with cardiotoxic agents, should have a clinical risk assessment
of cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, patients should be class 2B or better. Patients must not
have evidence of current uncontrolled cardiovascular conditions, including
hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or
myocardial infarction within 6 months prior to Step 1 registration
• STEP 1 •Patient may have a history of current or previous deep vein thrombosis (DVT)
or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation
as prophylaxis if they are not currently on full-dose anticoagulation
• STEP 1 •Patients with a history of chronic obstructive pulmonary disease (COPD) must
have FEV1 testing done within 28 days prior to Step 1 registration and the forced
expiratory volume in 1 second (FEV1) must be > 50% of predicted normal
• STEP 2 •Institution must have received Tracking (MRD) test results from Adaptive
Biotechnologies
• STEP 2 •Patient must have completed the Step 1 Induction phase of this protocol
without experiencing progression
• STEP 2 •Patient must be registered to Step 2 within 8 weeks of completing Step 1
Induction Treatment, counting from last day of completion of last cycle
• STEP 2 •Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if
secondary to pain)
• STEP 2 •Any adverse event(s) related to Step 1 Induction Treatment must have resolved
to grade 2 or less
• STEP 2 •Hemoglobin >= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
• STEP 2 •Platelet count >= 50,000/mm^3 (obtained within 14 days prior to Step 2
randomization)
• STEP 2 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Calculated creatinine clearance >= 30 mL/min (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Total bilirubin =< 1.5 x ULN (Institutional upper limit of normal) (obtained
within 14 days prior to Step 2 randomization)
• STEP 2 •ALT and AST < 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
• STEP 0 •Patient must not have any known allergies, hypersensitivity, or intolerance
to corticosteroids, monoclonal antibodies or human proteins, or their excipients
(refer to respective package inserts or Investigator's Brochure), or known sensitivity
to mammalian-derived products
• STEP 1 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 1 registration to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)
• STEP 1 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception). Men must not expect to father children by practicing true abstinence
from sexual intercourse for the duration of their participation in the study (periodic
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and
withdrawal are not acceptable methods of contraception) OR use a latex condom during
sexual contact with a female of child bearing potential while participating in the
study and for at least 3 months after the last dose of protocol treatment even if they
have had a successful vasectomy. Men must also agree to abstain from donating sperm
while on study treatment and for 3 months after the last dose of protocol treatment
even if they have had a successful vasectomy. Both women and men must both agree to
abstain from donating blood during study participation and for at least 28 days after
the last dose of protocol treatment
• STEP 1 •Patient must not have peripheral neuropathy >= grade 2 on clinical
examination or grade 1 with pain at time of Step 1 registration
• STEP 1 •Patient must not have any serious medical or psychiatric illness that could,
in the investigator's opinion, potentially interfere with the completion of treatment
according to this protocol
• STEP 1 •Patient must not have moderate or severe persistent asthma within the past 2
years, or uncontrolled asthma of any classification
• NOTE: Patients who currently have controlled intermittent asthma or controlled
mild persistent asthma are allowed to register
• STEP 1 •Patient must not receive any other concurrent chemotherapy, or any ancillary
therapy considered investigational while on this protocol
• NOTE: Bisphosphonates are considered to be supportive care rather than therapy,
and are thus allowed while on protocol treatment
• STEP 2 •Patient must not have received any non-protocol therapy outside of the
assigned Step 1 Induction treatment including stem cell transplant
• STEP 2 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months).
• STEP 2 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception).
Men must not expect to father children by practicing true abstinence from sexual
intercourse for the duration of their participation in the study (periodic abstinence
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not
acceptable methods of contraception) OR use a latex condom during sexual contact with a
female of child bearing potential while participating in the study and for at least 3
months after the last dose of protocol treatment even if they have had a successful
vasectomy. Men must also agree to abstain from donating sperm while on study treatment and
for 3 months after the last dose of protocol treatment even if they have had a successful
vasectomy. Both women and men must both agree to abstain from donating blood during study
participation and for at least 28 days after the last dose of protocol treatment
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, Multiple Myeloma
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