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.
Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease (MAC2v3)
NTM therapy consists of a multi-drug macrolide based regimen for 18-24 months. Treated
patients frequently experience debilitating side effects, and many patients delay the start
of antibiotic treatment due to these risks. Common side effects include nausea, diarrhea, and
fatigue, and rare but serious toxicities include ocular toxicity, hearing loss, and
hematologic toxicity. To date, most of the evidence underlying the current treatment
recommendations has come from observational studies in which either a macrolide has been
combined with rifampin and ethambutol, or in some cases combined with ethambutol alone. The
proposed study will answer whether a third drug is necessary or whether taking two drugs can
increase tolerability without a substantial loss of efficacy.
Christopher Saddler
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03672630
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Inclusion Criteria:
• Culture positive pulmonary MAC meeting ATS/IDSA disease criteria
• Age over 18 years
• Ability to provide informed consent
Exclusion Criteria:
• Fibrocavitary disease
• Planned surgery for MAC disease
• Patients who have cumulatively taken 6 weeks or more of multi-drug antimicrobial
treatment for MAC
• Patients who are currently taking or have taken multi-drug antimicrobial treatment for
NTM within the prior 30 days
• Diagnosis of Cystic fibrosis
• Diagnosis of HIV
• History of solid organ or hematologic transplant
• Significant drug-drug interaction not clinically manageable in the opinion of the
investigator
• Contraindication to any component of the study treatment regimen
Mycobacterium Avium Complex, Nontuberculous Mycobacterium Infection, Infection due to other mycobacteria, Other, Infections, Immune System & Allergies
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
A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma
This phase II/III trial studies the side effects of nivolumab and ipilimumab when given
together with or without sargramostim and to see how well they work in treating patients with
stage III-IV melanoma that cannot be removed by surgery (unresectable) and that may have
spread from where it first started to nearby tissue, lymph nodes, or distant parts of the
body (advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Colony-stimulating factors, such as sargramostim, may
increase the production of white blood cells. It is not yet known whether nivolumab and
ipilimumab are more effective with or without sargramostim in treating patients with
melanoma.
Mark Albertini, M.D.
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT02339571
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Inclusion Criteria:
• All patients must be >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
• Patients must have known BRAF mutational status of tumor; wild-type (WT) or mutated,
prior to randomization
• Patients must not be pregnant or breast-feeding due to use of cytotoxic immunotherapy
and risk of teratogenic side effects; all patients of childbearing potential must have
a blood test or urine study within 2 weeks prior to randomization to rule out
pregnancy; a patient of childbearing potential is anyone, 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)
• Patients must not conceive or father children by using accepted and effective
method(s) of contraception or by abstaining from sexual intercourse from the time of
study registration and continuing (for patients of child bearing potential) for at
least 5 months after the last dose of protocol treatment; patients of childbearing
potential must also not donate eggs during this same time period
• Patients must have unresectable stage III or stage IV melanoma according to American
Joint Committee on Cancer (AJCC) version (v)7; patients must have histological or
cytological confirmation of melanoma that is metastatic or unresectable and clearly
progressive
• Patients must have measurable disease per RECIST 1.1 criteria; all sites of disease
must be evaluated within 4 weeks prior to randomization
• Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon,
BRAF, or MEK agents). Patients may have had prior anti-CTLA-4 in the adjuvant setting,
if at least one year from last dose of treatment has passed prior to beginning
treatment. Patients may have had any prior anti-PD-1 or anti-PD-L1 agent in the
adjuvant setting, if at least one year from last dose of treatment has passed prior to
beginning treatment
• Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the
metastatic setting
• Patients must have discontinued chemotherapy, immunotherapy or other investigational
agents used in the adjuvant setting >= 4 weeks prior to randomization and recovered
from adverse events due to those agents; mitomycin and nitrosoureas must have been
discontinued at least 6 weeks prior to entering the study; patients must have
discontinued radiation therapy >= 2 weeks prior to entering the study and recovered
from any adverse events associated with treatment; prior surgery must be >= 4 weeks
from randomization and patients must be fully recovered from post-surgical
complications
• Patients must not receive any other investigational agents while on study or within
four weeks prior to randomization
• Patient must not have received any live vaccine within 30 days prior to randomization,
while participating in the study, and for 4 weeks (28 days) after the last dose of
protocol treatment; live vaccines include, but are not limited to, the following:
measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin
(BCG), and typhoid (oral) vaccine; patients are permitted to receive inactivated
vaccines and any non-live vaccines including those for the seasonal influenza and
coronavirus disease 19 (COVID-19) (Note: intranasal influenza vaccines, such as
Flu-Mist (registered trademark) are live attenuated vaccines and are not allowed); if
possible, it is recommended to separate study drug administration from vaccine
administration by about a week (primarily, in order to minimize an overlap of adverse
events)
• Patients are ineligible if they have any currently active central nervous system (CNS)
metastases; patients who have treated brain metastases (with either surgical resection
or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging
(MRI) or contrast computed tomography (CT) scan for at least 4 weeks following
treatment and within 4 weeks prior to randomization are eligible; patients must not
have taken any steroids =< 14 days prior to randomization for the purpose of managing
their brain metastases; patients with only whole brain irradiation for treatment of
CNS metastases will be ineligible
• Patients must not have other current malignancies, other than basal cell skin cancer,
squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in
situ of the breast; patients with other malignancies are eligible if they have been
continuously disease-free for > 3 years prior to the time of randomization
• White blood count >= 3,000/uL (obtained within 4 weeks prior to randomization)
• Absolute neutrophil count (ANC) >= 1,500/uL (obtained within 4 weeks prior to
randomization)
• Platelet count >= 100,000/uL (obtained within 4 weeks prior to randomization)
• Hemoglobin >= 9 g/dL (obtained within 4 weeks prior to randomization)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance
(CrCl) >= 40 ml/min (obtained within 4 weeks prior to randomization)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x
ULN for patients with documented liver metastases) (obtained within 4 weeks prior to
randomization)
• Alkaline phosphatase =< 2 x ULN (=< 5 x ULN for patients with known liver involvement
and =< 7 x ULN for patients with known bone involvement) (obtained within 4 weeks
prior to randomization)
• Total bilirubin =< 1.5 x ULN except patients with normal direct bilirubin; those
patients with known Gilbert's syndrome must have total bilirubin < 3 x ULN (obtained
within 4 weeks prior to randomization)
• Serum lactate dehydrogenase (LDH) =< 10 X ULN (obtained within 4 weeks prior to
randomization)
• Patients must not have any serious or unstable pre-existing medical conditions (aside
from malignancy exceptions specified above), including but not limited to, ongoing or
active infection requiring parenteral antibiotics on day 1, history of bleeding
diathesis or need for concurrent anticoagulation (international normalized ratio [INR]
=< 1.5 and partial thromboplastin time [PTT] within 1.1 x ULN), or psychiatric
illness/social situations that would limit compliance with study requirements,
interfere with patient's safety, or obtaining informed consent
• Patients with human immunodeficiency virus (HIV) infection are ineligible; due to the
mechanism of action of ipilimumab and GM-CSF, activity and side effects in an immune
compromised patient are unknown
• Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection are not eligible; patients with cleared HBV and HCV (0 viral load) infection
will be allowed
• Patients must not have autoimmune disorders or conditions of immunosuppression that
require current ongoing treatment with systemic corticosteroids (or other systemic
immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or
continuous use of topical steroid creams or ointments or ophthalmologic steroids; a
history of occasional (but not continuous) use of steroid inhalers is allowed;
replacement doses of steroids for patients with adrenal insufficiency are allowed;
patients who discontinue use of these classes of medication for at least 2 weeks prior
to randomization are eligible if, in the judgment of the treating physician
investigator, the patient is not likely to require resumption of treatment with these
classes of drugs during the study
• Exclusion from this study also includes patients with a history of symptomatic
autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis
[scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis
[e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin
(e.g., Guillain-Barre syndrome and myasthenia gravis); other CNS autoimmune disease
(e.g., multiple sclerosis)
• Patients with autoimmune hypothyroid disease or type I diabetes on replacement
treatment are eligible
• Patients must not have a history of inflammatory bowel disease or diverticulitis
(history of diverticulosis is allowed)
• Patients must not have other significant medical, surgical, or psychiatric conditions
or require any medication or treatment that in the opinion of the investigator may
interfere with compliance, make the administration of the study drugs hazardous or
obscure the interpretation of adverse events (AEs), such as a condition associated
with frequent diarrhea; patients must not have an active infection requiring current
treatment with parenteral antibiotics
Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7, Melanoma, Skin, Melanoma/Skin cancer
Testing Docetaxel-Cetuximab or the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy and Radiation Therapy in High-Risk Head and Neck Cancer
This phase II/III trial studies how well radiation therapy works when given together with
cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with
high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous
cell). Specialized radiation therapy that delivers a high dose of radiation directly to the
tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in
chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of
tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a
monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.
Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
spread. The purpose of this study is to compare the usual treatment (radiation therapy with
cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy,
and using the usual treatment plus an immunotherapy drug, atezolizumab.
Paul Harari, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT01810913
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Inclusion Criteria:
• PHASE II INCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
• Pathologically (histologically or cytologically) proven diagnosis of head and neck
squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx
(p16 negative), larynx, or hypopharynx
• Patients must have undergone gross total surgical resection of high-risk oral cavity,
oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to
registration; Note: patients may have biopsy under general anesthesia in an operating
room followed by definitive ablative cancer surgery representing gross total
resection; the gross total resection has to be done within 63 days prior to
registration; if, however, patients have ablative resection but shortly recur or are
determined to have persisting disease requiring re-resection to achieve gross total
resection, then the patient is not eligible
• Patients must have at least 1 of the following high-risk pathologic features:
extracapsular nodal extension or invasive cancer at the primary tumor resection margin
(tumor on ink)
• Pathologic stage III or IV HNSCC, including no distant metastases, based upon the
following minimum diagnostic workup:
• General history and physical examination by a radiation oncologist and/or medical
oncologist within 84 days prior to registration;
• Examination by an ear nose throat (ENT) or head & neck surgeon prior to surgery;
a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if
appropriate, is recommended but not required; intra-operative examination is
acceptable documentation
• Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT)
(with contrast) or CT/positron emission tomography (PET) (with contrast) and/or
an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2)
within 84 days prior to surgery; Note: this imaging data (diagnostic
pre-operative scan showing gross disease) is to be submitted in Digital Imaging
and Communications in Medicine (DICOM) format via TRIAD; the report is to be
uploaded into Rave
• Chest CT scan (with or without contrast) or CT/PET that includes the chest (with
or without contrast) either within 84 days prior to surgery or within 120 days
prior to registration; Note: if the CT/PET with or without contrast is done
within 84 days prior to surgery, it fulfills the chest imaging requirement
• Zubrod performance status of 0-1 within 14 days prior to registration
• Age >= 18
• Absolute granulocyte count (AGC) >= 1,500 cells/mm^3 (obtained within 14 days prior to
registration on study)
• Platelets >= 100,000 cells/mm^3 (obtained within 14 days prior to registration on
study)
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve
hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Total bilirubin < 2 x institutional upper limit of normal (ULN) within 14 days prior
to registration
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x institutional
ULN within 14 days prior to registration
• Serum creatinine institutional ULN within 14 days prior to registration or; creatinine
clearance (CC) >= 50 ml/min within 14 days prior to registration determined by 24-hour
collection or estimated by Cockcroft-Gault formula
• Negative urine or serum pregnancy test within 14 days prior to registration for women
of childbearing potential
• The following assessments are required within 14 days prior to registration: sodium
(Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and
albumin; Note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive
corrective magnesium supplementation but should continue to receive either
prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g.,
magnesium oxide) at the investigator's discretion
• Patients with feeding tubes are eligible for the study
• Women of childbearing potential and male participants who are sexually active must
agree to use a medically effective means of birth control
• Patient must provide study specific informed consent prior to study entry, including
consent for mandatory tissue submission for epidermal growth factor receptor (EGFR)
analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis
• PHASE III: Pathologically (histologically or cytologically) proven diagnosis of head
and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips),
oropharynx (p16 negative), larynx, or hypopharynx
• PHASE III: Patients with oropharyngeal cancer must have p16-negative based on central
review prior to Step 2 registration; all patients with oropharyngeal primary must
consent for mandatory tissue submission for central p16 confirmation
• PHASE III: Patients must have undergone gross total surgical resection of high-risk
oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to
registration; note: patients may have biopsy under general anesthesia in an operating
room followed by definitive ablative cancer surgery representing gross total
resection; the gross total resection has to be done within 63 days prior to
registration; if, however, patients have ablative resection but shortly recur or are
determined to have persisting disease requiring re-resection to achieve gross total
resection, then the patient is not eligible
• PHASE III: Patients must have at least 1 of the following high-risk pathologic
features: extracapsular nodal extension or invasive cancer at the primary tumor
resection margin (tumor on ink or tumor in a final separately submitted margin)
• PHASE III: Pathologic stage III or IV HNSCC (American Joint Committee on Cancer [AJCC]
7th edition), including no distant metastases, based upon the following minimum
diagnostic workup:
• General history and physical examination by a radiation oncologist or medical
oncologist within 84 days prior to registration;
• Examination by an ENT or head & neck surgeon prior to surgery; a
laryngopharyngoscopy (mirror or fiberoptic or direct procedure), if appropriate,
is recommended but not required. Intra-operative examination is acceptable
documentation.
• Pre-op Imaging of the head and neck: A neck CT (with contrast and of diagnostic
quality) or PET/CT (with contrast and of diagnostic quality) and/or an MRI of the
neck of diagnostic quality (T1 with gadolinium and T2) within 84 days prior to
surgery; Note: this imaging data (diagnostic pre-operative scan showing gross
disease) is to be submitted in DICOM format via TRIAD. The report is to be
uploaded into Rave.
• Chest CT scan (with or without contrast) or PET/CT that includes the chest (with
or without contrast) either within 84 days prior to surgery or within 120 days
prior to registration; Note: If the PET/CT with or without contrast is done
within 84 days prior to surgery, it fulfills the chest imaging requirement
• PHASE III: Zubrod performance status of 0-1 within 14 days prior to registration
• PHASE III: Leukocytes >= 2,500 cells/mm^3 (obtained within 14 days prior to
registration on study)
• PHASE III: Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 14
days prior to registration on study)
• PHASE III: Platelets >= 100,000 cells/mm^3 (obtained within 14 days prior to
registration on study)
• PHASE III: Hemoglobin >= 8.0 g/dL (Note: The use of transfusion or other intervention
to achieve Hgb >= 8.0 g/dL is acceptable) (obtained within 14 days prior to
registration on study)
• PHASE III: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
(however, patients with known Gilbert disease who have serum bilirubin level =< 3 x
institutional ULN may be enrolled) (within 14 days prior to registration)
• PHASE III: AST or ALT =< 3 x institutional ULN (within 14 days prior to registration)
• PHASE III: Alkaline phosphatase =< 2.5 x institutional ULN (within 14 days prior to
registration)
• PHASE III: Creatinine clearance (CrCl) >= 50 mL/min within 14 days prior to
registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
• PHASE III: Patients with feeding tubes are eligible for the study
• PHASE III: Negative urine or serum pregnancy test within 14 days prior to registration
for women of childbearing potential
• PHASE III: All patients must provide study specific informed consent prior to study
entry
• PHASE III: Patients positive for human immunodeficiency virus (HIV) are allowed on
study, but HIV-positive patients must have:
• A stable regimen of highly active anti-retroviral therapy (HAART);
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections;
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard
polymerase chain reaction (PCR)-based tests
Exclusion Criteria:
• PHASE II EXCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in
situ of the breast, oral cavity, or cervix are all permissible) are permitted even if
diagnosed and treated < 3 years ago
• Patients with simultaneous primaries or bilateral tumors are excluded, with the
exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
resected differentiated thyroid carcinoma, who are eligible
• Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the
study cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
6 months prior to registration
• Transmural myocardial infarction within 6 months prior to registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration
• Idiopathic pulmonary fibrosis or other severe interstitial lung disease that
requires oxygen therapy or is thought to require oxygen therapy within 1
year prior to registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for coagulation parameters are not required
for entry into this protocol
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease and Control and Prevention (CDC) definition; note: human
immunodeficiency virus (HIV) testing is not required for entry into this
protocol; the need to exclude patients with AIDS from this protocol is
necessary because the treatments involved in this protocol may be
significantly immunosuppressive; protocol-specific requirements may also
exclude immuno-compromised patients.
• Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events
[CTCAE], version [v.] 4):
• Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5
mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
• Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14 mmol/L)
• Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention
to normalize levels
• Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
• Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
• Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic
• Prior allergic reaction to cetuximab
• PHASE III: Prior invasive malignancy (except non-melanomatous skin cancer) unless
disease free for a minimum of 1095 days (3 years) with the following exceptions: T1-2,
N0, M0 resected differentiated thyroid carcinoma; Note that noninvasive cancers (For
example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even
if diagnosed and treated < 3 years ago
• PHASE III: Patients with simultaneous primaries or bilateral tumors are excluded, with
the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
resected differentiated thyroid carcinoma, who are eligible
• PHASE III: Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted
therapy (such as anti-EGF therapy), or immune therapy for the study cancer; note that
prior chemotherapy for a different cancer is allowable, however, a prior anti-PD-1,
anti-PD-L1, or anti-PD-L2 agent is not permitted
• PHASE III: Prior radiotherapy to the region of the study cancer that would result in
overlap of radiation therapy fields
• PHASE III: Severe, active co-morbidity, defined as follows:
• 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 within 6
months prior to registration
• Transmural myocardial infarction within 6 months prior to registration;
• Severe infections within 4 weeks prior to registration including, but not limited
to, hospitalization for complications of infection, bacteremia, or severe
pneumonia;
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration; Note: Patients receiving prophylactic antibiotics (e.g., for
prevention of a urinary tract infection or chronic obstructive pulmonary disease
exacerbation) are eligible.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of
registration;
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan. History of radiation pneumonitis in a prior radiation field
(fibrosis) is permitted, provided that field does not overlap with the planned
radiation field for the study cancer;
• Patients with active tuberculosis (TB) are excluded;
• Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease;
• Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV RNA.
• History of allogeneic bone marrow transplantation or solid organ transplantation.
• A diagnosis of immunodeficiency:
• Acquired immune deficiency syndrome (AIDS) based upon current CDC
definition; note: HIV testing is not required for entry into this protocol;
the need to exclude patients with AIDS from this protocol is necessary
because the treatments involved in this protocol may be significantly
immunosuppressive.
• Is receiving treatment with systemic immunosuppressive medications (including,
but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks
prior to registration.
• Note: Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be
enrolled.
• Note: The use of inhaled corticosteroids and mineralocorticoids (e.g.,
fludrocortisone) for patients with orthostatic hypotension or adrenocortical
insufficiency is allowed.
• History or risk of autoimmune disease, including, but not limited to, systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular
thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis,
Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
glomerulonephritis.
• Patients with a history of autoimmune hypothyroidism who are asymptomatic
and/or are on a stable dose of thyroid replacement hormone are eligible.
• Patients with controlled Type 1 diabetes mellitus on a stable insulin
regimen are eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis
would be excluded) are permitted provided that they meet the following
conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out
ocular manifestations
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
• No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)
• PHASE III: Grade 3-4 electrolyte abnormalities (CTCAE, v. 4) within 14 days prior to
registration:
• Serum calcium (ionized or adjusted for albumin) < 7 mg/dL (1.75 mmol/L) or > 12.5
mg/dL (> 3.1 mmol/L) despite intervention to normalize levels;
• Glucose < 40 mg/dL (< 2.2 mmol/L) or > 250 mg/dL (> 14 mmol/L);
• Magnesium < 0.9 mg/dL (< 0.4 mmol/L) or > 3 mg/dL (> 1.23 mmol/L) despite
intervention to normalize levels;
• Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels;
• Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels.
• PHASE III: Pregnancy or women of childbearing potential and men who are sexually
active and not willing/able to use medically acceptable forms of contraception for up
to 5 months from last study treatment; this exclusion is necessary because the
treatment involved in this study may be significantly teratogenic. Women who are
breastfeeding and unwilling to discontinue are also excluded
• PHASE III: History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
• PHASE III: Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use
of bisphosphonate therapy for other non-oncologic reasons (e.g., osteoporosis) is
allowed
• PHASE III: Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) for
non-oncologic reasons who cannot discontinue it before registration
• PHASE III: Patients with known distant metastatic disease are excluded
• PHASE III: Known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies
• PHASE III: Major surgical procedure within 28 days prior to registration or
anticipation of need for a major surgical procedure during the course of the study
• PHASE III: Administration of a live, attenuated vaccine within 4 weeks prior to
registration or anticipation that such a live, attenuated vaccine will be required
during the study and for patients receiving atezolizumab, up to 5 months after the
last dose of atezolizumab.
• Influenza vaccination should be given during influenza season only (approximately
October to March). Patients must not r
Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma, Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
Observational Study of Pediatric Rheumatic Diseases: The CARRA Registry
Continuation of the CARRA Registry as described in the protocol will support data collection
on patients with pediatric-onset rheumatic diseases. The CARRA Registry will form the basis
for future CARRA studies. In particular, this observational registry will be used to answer
pressing questions about therapeutics used to treat pediatric rheumatic diseases, including
safety questions.
Dominic Co, MD, PhD
All
up to 21 Years old
N/A
This study is NOT accepting healthy volunteers
NCT02418442
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Inclusion Criteria:
1. Onset of rheumatic disease prior to age 16 years for JIA and onset prior to age 19
years for all other rheumatic diseases (see appendix A).
2. Subject (and/or parent/legal guardian when required) is able to provide written
informed consent and willing to comply with study procedures.
3. Subject and/or parent/legal guardian is willing to be contacted in the future by study
staff.
Exclusion Criteria:
1. Greater than 21 years of age at the time of enrollment.
Rheumatic Joint Disease, Rheumatic Diseases [C05], Other
Patients Treated for Chronic Granulomatous Disease (CGD) Since 1995
Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone
marrow transplantation (BMT) has been shown to be curative. However the risks of
transplantation are high and not all patients with CGD may need to undergo this high risk
procedure. This study will determine the long term medical condition and daily functioning of
participants with CGD after a transplant and if possible, compare these results to
participants who do not undergo a transplant.
Kenneth Desantes, M.D.
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT02082353
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Inclusion Criteria:
• Participant Inclusion Criteria (Part 1 •Longitudinal Analysis)
• CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After
1988
1. CGD Patients will be Defined by both Defective Neutrophil NADPH Oxidase
Function and by Clinical History Consistent with CGD
Patients must have both of:
A functional assay demonstrating abnormal NADPH oxidase function (see A
below); AND Clinical history consistent with CGD (see B below).
*************************************************************************
Patients must have both "A" and "B":
A. Function: Assays of NADPH Oxidase Function
I. Dihydrorhodamine (DHR) Assay:
• Blood sample was obtained at a time when patient was clinically stable
and not critically ill, with control samples performed simultaneously
indicating a qualified assay; and
• Assay unequivocally demonstrates CGD with an stimulation index (SI) SI
< 35 or equivalent. Assay report, including mean fluorescence intensity
(MFI) from unstimulated and stimulated samples and gating strategy,
must be de-identified and provided. OR
II. Nitroblue Tetrazolium Oxidation Test (NBT):
o Diagnostic of CGD (reported as reduced granulocyte oxidative response).
Report must be de-identified and provided. AND
B. Clinical History: One or More of the Following:
• Severe and/or recurrent infection (liver, perirectal or lung abscess;
pneumonia; adenitis; or osteomyelitis) due to, for example,
Staphylococcus aureus, Burkholderia sp, Serratia marcescens,
non-albicans Candida sp, Aspergillus sp or other mold; or Nocardia sp
or other deep tissue infection characteristic of CGD
• Sterile granulomatous disease in respiratory, gastrointestinal or
urogenital tracts; or Crohn's disease-like colitis
• A family history consistent with either X-linked or autosomal recessive
CGD
In cases where either functional assay (A) or history (B) is equivocal, one
or more of the following may be used to confirm a diagnosis of CGD:
C. Absent or significantly reduced in expression or abnormal size of any of
the 5 phox components (gp91 phox, p47 phox, p22 phox, p67phox, and p40phox)
of NADPH oxidase, by either:
• Western blot
• Northern blot OR D. Mutation in a gene encoding one of the 5 phox
components (gp91 phox, p47 phox, p22 phox, p67 phox, and p40 phox) of
NADPH oxidase that is predictive of a decreased or absent oxidative
burst. (Nonsense, frameshift, or previously described missense mutation
associated with CGD).
Molecular Diagnosis is Desirable In addition, molecular diagnosis (gene
sequencing and expression analysis) of CGD is desirable and should be
performed when possible.
2. Further Characterization of Oxidase Level, Longitudinal Study, Prospective
Cohort Patients who are to undergo transplantation during the study period
must be further characterized as oxidase-null or oxidase positive by level
of oxidase production by either:
• DHR assay stimulation Index: where SI ≤ 2.5 will be classified as
oxidase-null CGD. Those with SI > 2.5 will be classified as oxidase
positive CGD. A single validated test that is accepted by the PID-CGD
Review Panel is adequate, but testing on two occasions for validation
is desirable. OR
• Ferricytochrome C reduction assay of granulocytes with O2 < 2.3 nmoles
/106 cells/h classified as oxidase-null CGD. A single validated test
that is accepted by the PID-CGD Review Panel is adequate, but testing
on two occasions for validation is desirable.
OR
o Genetic sequencing reporting a mutation that is unequivocally associated
to absent oxidase production. (e.g. null mutations) will be classified as
oxidase-null CGD (See discussion in Appendix I for how family history,
genotype and CGD mutation information will be applied to assigning patients
lacking any quantitative oxidase activity measurements to residual
oxidase-null or residual oxidase-positive groups).
3. Longitudinal Study, Retrospective Cohort Patients who have already been
transplanted will be included regardless of whether further characterization
by oxidase level (or genotype/mutation data) is possible or not.
• Non-Transplanted CGD Patients with Birth Year In or After 1988 A non-transplant
(conventional therapy) group of CGD subjects will be enrolled in the longitudinal
study. The non-transplant subjects will be selected from the potentially eligible
(retrospective) patient cohort with diagnosis of CGD treated with conventional
non-transplant therapy. Participating sites will enter their entire retrospective
cohort of CGD patients having birth year in or after 1988 into the registration
cohort for this protocol. Baseline for both non-transplant subjects and HCT
subjects for the purpose of comparing survival will be the year of birth.
However, for non-transplant subjects, many of the detailed analyses such as
infection and autoimmune complication rates will be assessed in the year
preceding the date of last contact.
• Participant Inclusion Criteria (Part 2 •Cross-Sectional Analysis) To participate in
the Cross-Sectional Analysis, patients must have previously been enrolled into the
Longitudinal Analysis of Protocol 6903. All transplanted subjects in the
Cross-Sectional Analysis are surviving and shall have at least 3 years of follow-up
post-transplant to be included. Non-transplanted CGD subjects will become eligible for
consideration for the Cross-Sectional Analysis if they were eligible and enrolled in
the retrospective cohort of the Longitudinal Analysis, and if/when they are > 3 years
post-diagnosis of CGD. Provision of written informed consent will be required for
inclusion in the Cross-Sectional Analysis.
Exclusion Criteria:
• Participant Exclusion Criteria (Longitudinal and Cross- Sectional Analyses)
• Presence of other primary immunodeficiency syndromes that do not meet the
clinical and laboratory criteria for CGD.
• Rac2 Deficiency
• Myeloperoxidase Deficiency (MPO Deficiency)
• Glutathione deficiency
• Leukocyte adhesion deficiency syndrome
• Non-transplant subjects:
• The above exclusions pertain.
• In addition, non-transplant subjects will be excluded if the only assessment of
oxidase function available is the nitroblue tetrazolium (NBT) test (a
non-quantitative test).
Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990
Wiskott - Aldrich syndrome (WAS) is a rare serious medical condition that causes problems
both with the immune system and with easy bruising and bleeding. The immune abnormalities
cause patients with WAS to be very susceptible to infections. Depending on the specific type
of primary immune deficiency diseases, there are effective treatments, including antibiotics,
cellular therapy and gene therapy, but studies of large numbers of patients are needed to
determine the full range of causes, natural history, or the best methods of treatment for
long term success.
This multicenter study combines retrospective, prospective and cross-sectional analyses of
the transplant experiences for patients with WAS who have already received HCT since 1990, or
who will undergo Hematopoietic cell transplant (HCT) during the study period. The
retrospective and prospective portions of the study will address the impact of a number of
pre and post-transplant factors on post-transplant disease correction and ultimate benefit
from HCT and the cross-sectional portion of the study will assess the benefit of HCT 2 years
post-HCT in consenting surviving patients.
Kenneth Desantes, M.D.
Male
Not specified
NA
This study is NOT accepting healthy volunteers
NCT02064933
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Inclusion Criteria:
• WAS participants will be defined as males who have:
1. thrombocytopenia (< 100K) AND EITHER molecular diagnosis of WAS OR reduced WASP
expression; OR
2. thrombocytopenia (< 100K) AND positive family history consistent with WAS
diagnosis; OR
3. chronic thrombocytopenia (< 100K for minimum of 3 months) AND low mean platelet
volume (MPV below normal range for age) AND EITHER recurrent and/or severe
infections requiring treatment and/or eczema OR lack of antibody response to
polysaccharide antigens or low IgM.
• Longitudinal Analysis (Retrospective and Prospective)
1. Stratum A. Participants with WAS who have or will Receive HCT
• Participants with WAS who have received an HCT since January 1, 1990
2. Stratum B. Participants with WAS who have or will Receive Gene Transfer
• Participants in which the intention is to treat with gene transfer with
autologous modified cells
• Cross-Sectional Analysis (Strata A and B) 1. Participants with WAS who are surviving
and at least 2 years after the most recent HCT or gene therapy.
Exclusion Criteria:
• As this is a natural history study, for both the Longitudinal Analysis and the
Cross-Sectional Analysis we will not exclude any patients due to race or age who fit
the inclusion criteria.
Wiskott-Aldrich Syndrome, Immunologic Deficiency Syndromes [C20], Other
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
This research trial studies kidney tumors in younger patients. Collecting and storing samples
of tumor tissue, blood, and urine from patients with cancer to study in the laboratory may
help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify
biomarkers related to cancer.
Kenneth Desantes, M.D.
All
up to 29 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00898365
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Inclusion Criteria:
• Patients with the first occurrence of any tumor of the kidney identified on CT scan or
MRI are eligible for this study; histologic diagnosis is not required prior to
enrollment but is required for all patients once on study
• Eligible tumors include (but are not limited to):
• Nephroblastic tumors
• Nephroblastoma (Wilms' tumor) (favorable histology, anaplasia [diffuse,
focal])
• Nephrogenic rests and nephroblastomatosis
• Cystic nephroma and cystic partially differentiated nephroblastoma
• Metanephric tumors (metanephric adenoma, metanephric adenofibroma,
metanephric stromal tumor)
• Mesoblastic nephroma (cellular, classic, mixed)
• Clear cell sarcoma
• Rhabdoid tumor (any malignant rhabdoid tumor occurring outside the central
nervous system [CNS])
• Renal epithelioid tumors of childhood (papillary renal cell carcinoma, medullary
renal cell carcinoma, renal tumors associated with Xp11.2 translocations,
oncocytic renal neoplasms after neuroblastoma)
• Angiolipoma
• Ossifying renal tumor of infancy
• Patients with the first occurrence of the following tumors are also eligible:
• Extrarenal nephroblastoma or extrarenal neprogenic rests
• Malignant rhabdoid tumor occurring anywhere outside the central nervous system
• Required specimens, reports, forms, and copies of imaging studies must be available or
will become available for submission and the institution must intend on submitting
them as described in the protocol procedures
• For ALL patients, (with exception of bilateral, bilaterally predisposed, multicentric,
or unilateral tumor in solitary kidney planning to enroll without biopsy***), the
following submissions are required:
• A complete set of recut hematoxylin and eosin (H & E) slides (including from
sampled lymph nodes, if patient had upfront nephrectomy)
• * Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed favorable
histology Wilms tumor [FHWT] patients discovered to have diffuse anaplastic
Wilms tumor [DAWT] at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Representative formalin-fixed paraffin-embedded tissue block or if a block is
unavailable, 10 unstained slides from a representative block of tumor, if
available.
• Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed FHWT patients
discovered to have DAWT at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Institutional pathology report, Specimen Transmittal Form, and Pre-Treatment
Pathology Checklist
• Copies of images and institutional reports of CT and/or MRI abdomen and pelvis,
and Pre Treatment Imaging Checklist
• Copies of images and institutional report of chest CT for all malignant tumors
• Institutional surgical report(s) and Pre-Treatment Surgical Checklist
• CRFs: Staging Checklist and Metastatic Disease Form (if metastatic disease is
noted on imaging)
• Patients with bilateral, bilaterally predisposed, multicentric, or
unilateral tumor in solitary kidney planning to enroll without biopsy via
imaging only •these patients will not have central review or have a risk
assignment issued, but may contribute to specimen banking for future
research. However, if biopsy is done, tissue must be submitted as for other
renal tumors, and initial risk assignment will require pathology and
surgical rapid central reviews. The Specimen Transmittal Form and Pre
Treatment Pathology Checklist are also needed.
• Please note: if the above required items are not received within 120 days of
study enrollment, the patient will be considered off study
• 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
Individuals with a past diagnosis of severe combined immune deficiency (including many cases
of "leaky SCID", Omenn syndrome, and reticular dysgenesis) who have undergone blood and
marrow transplant, gene therapy, or enzyme replacement in the past may be eligible for this
study. The purpose of study is to look backwards at what has already been done in the. Over
800 patients with SCID are expected to be enrolled, making this one of the largest studies
ever to describe outcomes for patients with SCID treated at many different hospitals around
North America.
Kenneth Desantes, M.D.
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT01346150
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Inclusion Criteria:
Strata A, B, and C (Part 1 •Retrospective Study)-
• Individuals with Severe Combined Immune Deficiency (SCID) diagnosis who:
--were treated at a location participating in this consortium from 1968 until present,
and
--are not enrolled in RDCRN PIDTC-6901 (ClinicalTrials.gov ID: NCT01186913).
• Subjects who received HCT/GT/ERT prior to the present date are eligible for the
retrospective study. The enrollment criteria for subjects who died prior to definitive
therapy are the same as for Strata A, B and C.
Stratum A, Typical SCID:
• Individuals who meet the following inclusion criteria and who received HCT are
eligible for enrollment into Stratum A of the study:
• 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 (PHA) or cells of maternal origin present.
• If maternal cells are present but the patient does not meet criteria for very low
T cell function as defined, the assigned reviewers for the potential subject, and
if necessary, the full PID-SCID RP will review the laboratory report to determine
if criteria of maternal engraftment are met for Protocol 6902.
• Laboratory report of testing for maternal engraftment is required, for evaluation
by the PID-SCID RP.
Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis:
Individuals who meet the following criteria are eligible for enrollment into Stratum B of
the study:
Leaky SCID-
• Maternal lymphocytes tested for and not detected and,
• Either one or both of the following (a,b):
a) < 50% of lower limit of normal T cell function (as measured by response to PHA OR <
50% of lower limit of normal T cell function as measured by response to CD3/CD28
antibody, b) Absent or < 30% lower limit of normal proliferative responses to candida
and tetanus toxoid antigens postvaccination or exposure,
• AND at least one of the following (a through e):
1. Reduced number of CD3 T cells,
2. > 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 cells. c) Hypomorphic mutation in IL2RG in a male, or
homozygous hypomorphic mutation or compound heterozygosity with at least one
hypomorphic mutation in an autosomal SCID-causing gene.
d) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is
below the lower limit of normal.
e) Functional testing in vitro supporting impaired, but not absent, activity of the
mutant protein,
• AND does not meet criteria for Omenn Syndrome,
• AND does not have known selective loss of lymphocytes, Ataxia- Telangiectasia, or
congenital heart defect associated with lymphopenia, unless a SCID genotype is
also present.
Omenn Syndrome (OS):
• Generalized skin rash,
• Maternal engraftment tested for and not detected,
• Absent or low (up to 30% of normal) T cell proliferation to antigens to which the
patient has been exposed.
• If the proliferation to antigen was not performed, but at least 4 of the following 10
supportive criteria, at least one of which must be among those marked with an asterisk
(*) are present, the patient is eligible: hepatomegaly; splenomegaly; lymphadenopathy;
elevated IgE; elevated absolute eosinophil count; *oligoclonal T cells measured by
CDR3 length or flow cytometry >80% of CD4+ T cells are CD45RO+ ;*proliferation to PHA
is reduced <50% of lower limit of normal or SI <30; *proliferative response in mixed
leukocyte reaction is reduced to increment cpm < 20% or SI <20; hypomorphic mutation
to SCID causing gene; low TRECs and/or percentage of CD 4+/ RA+/CD31+; or
CD4+/RA+/CD62L+ cells below the lower limit of normal.
Reticular Dysgenesis (RD):
• Absence or very low number of T cells (CD3 T cells <300/microliter),
• No or very low (<10% of lower limit of normal) T cell function (as measured by
response to phytohemagglutinin (PHA),
• Severe congenital neutropenia (absolute neutrophil count <200/microliter),
• AND at least one of the following:
• Sensorineural deafness and/or absence of granulopoiesis at bone marrow
examination and/or a deleterious AK2 mutation,
• absence of granulopoiesis on bone marrow examination; a pathogenic mutation in
the adenylate kinase 2 (AK2) gene identified.
Stratum C, SCID with Non-HCT Treatments:
-Individuals who meet the following criteria and were treated with PEG-ADA or gene therapy
with autologous modified cells are eligible for enrollment into Stratum C (SCID with
non-HCT treatments) of the study-
•Any SCID patient previously treated with a thymus transplant (includes intention to treat
with HCT, as well as PEG-ADA ERT or gene therapy).
Strata A, B, and C (Part 2 •Cross-Sectional Study):
Patient inclusion criteria for the cross sectional study: Eligibility for Strata A, B and C
are the same as for the retrospective study except that all the patients in the
cross-sectional study are currently surviving and are at least 2 years post the most recent
class of therapy.
Exclusion Criteria:
Parts 1 and 2 •Retrospective and Cross-Sectional Studies -
• Lack of appropriate testing to rule out HIV infection after 1997 (p24 antigen or more
sensitive) or other cause of secondary immunodeficiency,
• Presence of DiGeorge syndrome,
• Most patients with other PIDs such as nucleoside phosphorylase deficiency, ZAP70
deficiency, CD40 ligand deficiency, NEMO deficiency, XLP, cartilage hair hypoplasia or
ataxia telangiectasia will not meet the inclusion criteria for Stratum A, B, or C
above; however, a patient with one of the above may meet the inclusion criteria for
Stratum B and if so will be included-
• MHC Class I and MHC Class II antigen deficiency are excluded,
• Metabolic conditions that imitate SCID or related disorders such as folate
transporter deficiency, severe zinc deficiency, transcobalamin deficiency.
SCID, ADA-SCID, XSCID, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis, Severe combined immunodeficiency [SCID] with reticular dysgenesis, Other
Protocol JDI2007-01 is an Expanded Access Protocol with therapeutic 131I-MIBG for patients
with neuroblastoma or pheochromocytoma / paraganglioma, who otherwise do not qualify for
available treatments, or where approved treatment is not commercially available.
Kenneth Desantes, M.D.
All
12 Months and over
Pilot/Feasibility
This study is NOT accepting healthy volunteers
NCT01590680
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INCLUSION CRITERIA:
1. Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on tumor
histopathology or elevated urine catecholamines with typical tumor cells in the bone
marrow, OR pheochromocytoma or paraganglioma (less than 12 years of age) not amenable
to curative surgery.
2. Age ≥12 months and able to cooperate with radiation safety restrictions during therapy
period with/without pharmacologic anxiolysis.
3. Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any time (any new lesion or an increase in size of >25% of a pre-existing
lesion). Disease evaluation must be completed within 8 weeks of study entry. If
possible, the disease evaluation should take place subsequent to any intervening
therapy; if intervening therapy does occur, evaluations should be done as clinically
indicated. If patient has received prior treatment with MIBG, they must have a
response or stable disease after the most recent MIBG infusion. Patient may have PD
after showing an initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).
4. Stem cells: Patients must have a hematopoietic stem cell product available for
re-infusion after 131I-MIBG treatment at doses of 12 mCi/kg. If no stem cells are
available, then the dose of 131I-MIBG should be <12 mCi/kg.
5. Prior Therapy: Patients may enter this study with or without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy, meeting the following criteria:
1. At least 2 weeks should have elapsed since any anti-tumor therapy and the patient
must meet certain hematologic criteria.
2. 3 months should have elapsed in the case of completing external beam radiation
for total abdominal, whole lung, total body irradiation (spot irradiation to
skull-based metastases is NOT a contraindication). Patients who receive localized
emergency radiation to sites of life-threatening or function-threatening disease
prior to or immediately after establishment of the definitive diagnosis are not
contraindicated for treatment on this protocol.
3. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued
a minimum of 24 hours prior to 131I-MIBG therapy.
4. Minimum of six weeks from previous 131I-MIBG therapy.
5. The lifetime cumulative injected activity should be evaluated by the Investigator
on a case-by-case basis with special attention to any recovery from past
131I-MIBG dose(s).
6. For patients who received a stem cell infusion for a previous 131I-MIBG therapy
but do NOT have remaining stored stem cells:
i. If the stem cell reinfusion was protocol driven but not based upon the development
of profound cytopenias (e.g. automatic stem cell reinfusion on Day 14), the patient is
eligible for retreatment with MIBG at a dose <12 mCi/kg at the investigators
discretion; ii. If the stem cell reinfusion was given based upon the development of
profound cytopenias, decisions for re-treatment with 131I-MIBG will require a
case-by-case evaluation by the Investigator.
6. Organ Function:
1. Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit
of normal.
2. Kidney function:
i. Serum Creatinine ≤ 2x upper limit of normal OR ii. 24-hr creatinine clearance OR
GFR ≥ 60 ml/min/1.73m2.
c. Hematologic Criteria: ANC ≥750/uL; Platelets ≥ 50,000/uL without transfusion if
stem cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells
available). Patient must be off myeloid growth factors for at least 24 hours. If the
patient has received prior treatment with MIBG, they may be thrombocytopenic, but
requiring no more than 2 platelet transfusions per week to maintain counts above
20,000/uL. Hemoglobin must be ≥ 10gm/dL (transfusion allowed) regardless of stored
stem cell availability.
d. Normal lung function, as manifested by no dyspnea at rest or exercise intolerance,
no oxygen requirement.
e. No clinically significant cardiac dysfunction.
7. Signed informed consent/assent has been obtained.
EXCLUSION CRITERIA:
1. Patients 12 years and older with iobenguane scan positive, unresectable, locally
advanced or metastatic pheochromocytoma or paraganglioma and marketed product is
available.
2. Patients eligible for the Phase II (OPTIMUM) trial.
3. Patients with disease of any major organ system that would compromise their ability to
withstand therapy. Any significant organ impairment should be discussed with the
Principal Investigator prior to patient entry.
4. Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential, who are
sexually active, must practice an effective method of birth control while
participating on this study, to avoid possible damage to the fetus . [e.g.
intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with
intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout
the study].
5. Patients who are on hemodialysis
6. Proteinuria, in the absence of urinary infection, within 4 weeks prior to the planned
treatment date is a relative contraindication to receiving therapy for patients with
pheochromocytoma/paraganglioma. Patients with pheochromocytoma/paraganglioma with any
clinically significant proteinuria must have a 24-hr urine protein determination. If
proteinuria is confirmed as being above the institutional upper limit of normal, the
patient is ineligible for MIBG therapy.
7. Patients with active infections that meet grade 3-4 according to the current version
of the NCI CTCAE.
8. Patients with known MIBG-avid parenchymal brain metastases are not eligible. (Patients
with leptomeningeal or skull-based metastases are eligible.)
Neuroblastoma, Pheochromocytoma, Paraganglioma, 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, 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
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
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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
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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
The purpose of the Registry is to provide continuing evaluation and periodic reporting of
safety and effectiveness of Medtronic market-released products. The Registry data is intended
to benefit and support interests of patients, hospitals, clinicians, regulatory bodies,
payers, and industry by streamlining the clinical surveillance process and facilitating
leading edge performance assessment via the least burdensome approach.
Micah Chan
All
Not specified
N/A
This study is NOT accepting healthy volunteers
NCT01524276
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Inclusion Criteria:
• Patient or legally authorized representative provides written authorization and/or
consent per institution and geographical requirements
• Patient has or is intended to receive or be treated with an eligible Medtronic product
• Patient within enrollment window relative to therapy initiation or meets criteria for
retrospective enrollment
Exclusion Criteria:
• Patient who is, or will be, inaccessible for follow-up
• Patient with exclusion criteria required by local law
• Patient is currently enrolled in or plans to enroll in any concurrent drug and/or
device study that may confound results
Cardiac Rhythm Disorders, Urological Disorders, Neurological Disorders, Cardiovascular Disorders, Digestive Disorders, Intracranial Aneurysm, Mechanical Circulatory Support, Respiratory Therapy, Aortic, Peripheral Vascular and Venous Disorders, Minimally Invasive Surgical Procedures, Diagnostic Techniques and Procedures, Surgical Procedures, Operative, Renal Insufficiency, Neurovascular, Coronary Artery Disease, Ear, Nose and Throat Disorder, Other
RejuvenAir® System Trial for COPD With Chronic Bronchitis (SPRAY-CB)
Chronic Obstructive Pulmonary Disease (COPD) is defined as an impaired ability to move air
within the lungs and is a major public health problem that is projected to rank fifth
worldwide in terms of disease burden and third in terms of mortality. Chronic bronchitis (CB)
is a common clinical phenotype within the umbrella of a COPD diagnosis and is classically
defined as chronic cough and sputum production for 3 months a year for 2 consecutive years2,
but many studies have used different definitions to define it- chronic cough and sputum
production for one year or cough and sputum production on most days of the week. CB is
associated with multiple clinical consequences, including; the worsening of lung function
decline, increasing risk of acute exacerbations of COPD, increased risk of developing
pneumonia, reduced health related quality of life, and an increase in all-cause mortality.
J Ferguson, MD
All
40 Years to 80 Years old
N/A
This study is NOT accepting healthy volunteers
NCT03893370
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Inclusion Criteria
• Males and females ≥40 to ≤80 years of age
• Subject is able to read, understand, and sign a written Informed Consent in order to
participate in the Study
• Subject has a diagnosis of chronic bronchitis (CB) and/or chronic obstructive
pulmonary disease (COPD) for a minimum of two years. (Chronic Bronchitis is defined
clinically as chronic productive cough for 3 months in each of 2 successive years in a
patient in whom other causes of productive cough have been excluded)
• Subject is classified as having a moderate or severe (GOLD 2/3) airflow obstruction
defined by a post-bronchodilator of ≥30% FEV1 to <80% predicted with a baseline
FEV1/FVC of <0.70
• Subject has a Baseline SGRQ of ≥50
• Subject demonstrates daily cough and significant mucus.
• Subject is being treated according to current medically accepted treatment guidelines
for chronic bronchitis for minimum of 3 months prior to enrollment into the study.
Subject agrees to continue maintenance pulmonary/COPD medications (GOLD standard
medications recommended) for the duration of the study
• Non-smoking for a minimum of 2 months prior to consent and agrees to continue not
smoking for the duration of the study
• Subject is able to adhere to and undergo 2 bronchoscopic procedures (cross over
subjects may undergo two additional bronchoscopic procedures, if they agree to
treatment), per hospital guidelines
• Subject demonstrates ability and willingness to use a daily eDiary
Exclusion Criteria
• Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring
medical treatment (with antibiotics and/or steroids) within 4 weeks prior of initially
planned study bronchoscopy
• Current diagnosis of Asthma
• Subject has Alpha-1 antitrypsin deficiency as defined by blood level <59 mg/dL
• Subject has other origins of respiratory disease aside from chronic bronchitis and
COPD
• Subject is using e-cigarettes, vaping or taking any inhaled substances not prescribed
by a physician
• Subject has untreatable or life threatening arrhythmias, inability to adequately
oxygenate during the bronchoscopy, or has acute respiratory failure
• Subject has bullous emphysema characterized as large bullae >30 millimeters on HRCT;
or subject has stenosis in the tracheobronchial system, tracheobronchomegaly,
trachea-bronchomalacia, amyloidosis or cystic fibrosis
• Subject has clinically significant bronchiectasis
• Subject has had a solid transplant procedure
• Subject has a known mucosal tear, has undergone prior lung surgery such as
pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery
• Subject has had a prior lung device procedure, including emphysema stent(s) implanted,
lung coils, valves, lung denervation, bronchial thermoplasty, cryotherapy or other
therapies
• Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin,
Coumadin, LMWH, heparin, clopidrogel (or equal)
• Subject has a serious medical condition, such as: uncontrolled coagulopathy or
bleeding disorder, congestive heart failure, uncontrolled angina, myocardial
infarction in the past year, renal failure, liver disease, cerebrovascular accident
within the past 6 months, uncontrolled diabetes, uncontrolled hypertension or
uncontrolled gastric reflux
• Subject is pregnant, nursing, or planning to get pregnant during study duration
• Subject has or is receiving chemotherapy or active radiation therapy within the past 6
months or is expected to receive chemotherapy during participation in this study
• Subject is or has been in another treatment study within 6 weeks of enrollment and
agrees to not participate in any other treatment studies for the duration of study
participation
• Subject has known sensitivity to medication required to perform bronchoscopy (such as
lidocaine, atropine, and benzodiazepines)
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
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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).
Stroke Prevention in the Wisconsin Native American Population
This project will develop a "Stroke Awareness Team" including training of Oneida Health
Service Coaches working in partnership with the UW team for a population-based health
awareness program. This team will develop a series of Oneida Nation Healthy Living and Stroke
Awareness Events (from now on health events) to provide education as to the severity of the
problem as well as our standard therapies for lifestyle change and risk factor avoidance.
This will include education of the healthy members of the tribe including the children to
identify signs of stroke and TIA in their elders as well as to develop healthy lifestyles at
the earliest of ages to influence the elders to modify their risks.
Robert Dempsey, MD
All
55 Years to 80 Years old
N/A
This study is also accepting healthy volunteers
NCT04382963
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Inclusion Criteria:
• Participants receiving health care through the Oneida Health Council Program
• Participants deemed to be at high risk for stroke by modified Framingham assessment of
medical history, including cerebral cardiovascular symptomatology, hypertension,
diabetes, smoking, BMI
• Willingness to participate in the study, including two-year follow-up
• Controls will be selected using the same criteria with the exception that upon
screening, they are not deemed to be at high risk for stroke.
Exclusion Criteria:
• Presence of established dementia
• Inability to participate in physical and exercise programs due to preexisting
disability
• Illiteracy
• Prior carotid procedure altering ultrasound finding
• Presence of medical condition precluding participation or follow-up over a two-year
period of time.
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
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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
Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study
This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation)
therapy works in comparison to standard-dose chemoradiation in treating patients with
early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and
capecitabine, 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. Radiation therapy
uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with
radiation therapy may kill more tumor cells. This study may help doctors find out if
lower-dose chemoradiation is as effective and has fewer side effects than standard-dose
chemoradiation, which is the usual approach for treatment of this cancer type.
Michael Bassetti, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04166318
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Inclusion Criteria:
• Patient must have histologically proven T1-2N0M0 invasive anal canal or anal margin
squamous cell carcinoma with tumors measuring =< 4 cm within 4 weeks prior to
randomization. This may include tumors of non-keratinizing histology such as basaloid,
transitional cell or cloacogenic histology. Patients with T1N0M0 anal margin squamous
cell carcinoma who underwent surgical excision with negative margins are not eligible
• Patients who are human immunodeficiency virus (HIV)-negative must not have lymph nodes
that are radiographically-concerning for cancer involvement using computed tomography
(CT) and positron emission tomography (PET)/CT-based criteria. Measurable disease is
not required
• Patients who are HIV-negative and do not have lymph nodes classified as lymph
node positive, but are felt to be borderline for cancer involvement must undergo
central imaging review
• NOTE: Patients requiring central imaging review will be pre-registered to
Arm S. Upon central confirmation of no lymph node involvement, eligible
patients may proceed to randomization on Step 1
• Patients will be considered to be lymph node (LN) positive and thereby not
eligible in this study if the lymph nodes meet any of the following criteria:
• Mesorectal, presacral, internal iliac or obturator LN with:
• Short axis measuring > 5 mm based on CT / magnetic resonance imaging
(MRI) OR
• Morphologic features of irregular border or central necrosis if
assessed on MRI and LN measures > 3 mm OR
• Fludeoxyglucose F-18 (FDG) uptake > blood pool (Deauville 3-5) based on
PET/CT
• External Iliac and common Iliac:
• Short-axis measuring > 1 cm based on CT / MRI OR
• Morphologic features of irregular border or central necrosis based on
CT / MRI OR
• FDG uptake > blood pool (Deauville 3-5) based on PET/CT
• Inguinal LN (superficial and deep) meeting any of the following criteria will be
ineligible unless an FNA is performed and resulting cytology is negative.
• Morphologic features of irregular border or central necrosis based on CT /
MRI
• FDG uptake > liver (Deauville 4) based on PET/CT.
• Patients who are HIV-negative and have inguinal lymph nodes that do not meet
the above criteria must undergo fine needle aspiration and have negative
histology to be eligible.
• Patients who are HIV-positive must have
• A CD4 count >= 300
• Confirmation of no lymph node involvement by central real-time review of imaging
• NOTE: Patients will be pre-registered to Arm S. Upon central confirmation of
no lymph node involvement, eligible patients may proceed to randomization on
Step 1
• Patient must have Eastern Cooperative Oncology Group (ECOG) •American College of
Radiology Imaging Network (ACRIN) performance status of 0-2
• Patient must have no history of prior radiation or chemotherapy for this malignancy
• Patient must not have had prior potentially curative surgery (i.e. abdominal-perineal
resection) for carcinoma of the anus
• Patients with excisional biopsy procedure are eligible provided there was tumor
involvement of the anal canal and/or anal verge prior to resection
• Patient must not be receiving any other standard anti-cancer therapy or experimental
agent concurrently with the study drugs
• Patient must not have intercurrent illness including, but not limited to, ongoing or
active infection or psychiatric/social situations that, in the judgement of the
investigator, would limit compliance with study requirements
• Patient must not have had significant cardiovascular disease including myocardial
infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary
artery disease, symptomatic congestive heart failure, or uncontrolled cardiac
arrhythmia within 6 months of randomization
• Patient must not have a history of a different malignancy unless they have been
disease-free for at least 2 years and are deemed by the investigator to be at low risk
of recurrence
• Individuals with the following cancers are eligible if diagnosed and treated
within the past 5 years: cervical cancer in situ and basal cell or squamous cell
carcinoma of the skin
• Patient must not have active autoimmune or connective disease
• Patients who are on anti-coagulation with warfarin within 2 weeks prior to
registration and are considering the use of capecitabine, must use an alternative
anti-coagulant
• NOTE: Low molecular weight heparin is permitted provided the patient's
prothrombin time (PT)/international normalized ratio (INR) is < 1.5
• Patients who will receive capecitabine and are on Dilantin for a seizure disorder must
have Dilantin levels checked weekly
• Hemoglobin > 10 g/dL (within 2 weeks prior to registration)
• Platelets >= 100,000/mm^3 (within 2 weeks prior to registration)
• Absolute neutrophil count >= 1500/mm^3 (within 2 weeks prior to registration)
• Serum creatinine must be < 1.5 X upper limit of normal (ULN), or calculated creatinine
clearance must be > 60 ml/min (within 2 weeks prior to registration)
• Total bilirubin must be < 2 X ULN (within 2 weeks prior to registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional
ULN (within 2 weeks prior to registration)
• Albumin >= 3.0 g/dL (within 2 weeks prior to registration)
• Women must not be pregnant or breast-feeding because the study treatment administered
may cause harm to an unborn fetus or breastfeeding child. 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 achieved menarche at some point, 2) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) 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)
• Women of childbearing potential and sexually active males must be strongly advised to
use accepted and effective method(s) of contraception or to abstain from sexual
intercourse for the duration of their participation in the study and for at least 6
months after the completion of treatment
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
Show full eligibility criteria
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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.
PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706
This study consists of 2 parts. Part 1 of the study is conducted to evaluate the efficacy,
safety, and tolerability of two doses of K0706 compared to placebo in subjects with early
Parkinson's Disease who are not receiving dopaminergic therapy. Part 2 is an optional long
term extension study for subjects who have completed week 40 of Part 1
Kathleen Shannon
All
50 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03655236
Show full eligibility criteria
Hide eligibility criteria
Part 1:
Inclusion criteria:
1. Males or females aged ≥ 50 years;
2. Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2;
3. Diagnosed with "Clinically Probable PD" according to the MDS clinical diagnostic
criteria, with documented diagnosis of PD per treating physician's records within
three years of the Screening visit. Disease severity according to modified Hoehn &
Yahr stage ≤ 2;
4. Projected to not required to start dopaminergic therapy within 9 months from Baseline;
Exclusion criteria:
1. Current, or within 60 days of Screening, use of any prescription, investigational, or
over the counter medication for the symptomatic treatment of PD or to slow the
progression of PD. Treatment with Monoamine Oxidase B (MAOB) inhibitors will be
allowed if the dose is stable for at least 30 days prior to Screening and subjects
agree to remain on it for the duration of the study;
2. Prior use of dopaminergic therapy (e.g., levodopa, dopamine agonist, amantadine) for
30 or more days any time in the past;
3. A diagnosis of a significant central or peripheral nervous system disease affecting
the subject's cognition or motor function at any time, such as another
neurodegenerative disorder, multiple sclerosis or stroke. This does not include
transient neurological deficits such as transient ischemic attacks or migraine aura;
4. A diagnosis of a medical condition that could interfere with interpretation of the
MDS-UPDRS during the trial (e.g., musculoskeletal disorders);
5. Contraindications to receiving an MRI;
6. Contraindications to receiving a DaT SPECT scan (e.g., hypersensitivity to the active
substance, any of the excipients, or iodine) if a new DaT SPECT scan is required for
the study;
7. Most recent DaT SPECT scan not compatible with PD (i.e., Scans Without Evidence of
Dopaminergic Deficit [SWEDD]) based on a central reading by a study physician;
8. MRI of the brain performed after onset of PD suggestive of secondary Parkinsonism
(e.g., subdural hematoma, normal pressure hydrocephalus, or infarcts of the basal
ganglia);
9. Severe tremors as defined by a score of "severe" on any of the MDS-UPDRS Parts 2 or 3
tremor severity (not constancy) items;
10. Montreal cognitive assessment score < 25
11. History of any surgery on the brain itself including deep brain stimulation for PD
(note this does not include surgeries on the skull that do not affect the brain, e.g.,
small meningioma removal);
12. History of hypersensitivity (e.g., bronchospasm, anaphylaxis, serious drug rash) to
contents of the study drug or other tyrosine kinase inhibitors;
13. Recent use of medications that can cause Parkinsonism and suspicion of the
investigator that it could have worsened the subject's Parkinsonism. This includes
neuroleptics (e.g., olanzapine, risperidone, haloperidol), some anti-nausea
medications (e.g., prochlorperizine, metoclopramide) and others (e.g., flunarizine,
methyldopa)
14. Use of medications that affect the dopaminergic system within 60 days of Screening.
This includes stimulants (e.g., methylphenidate, amphetamine derivatives, modafinil)
and Monoamine Oxidase A (MAOA) inhibitors (e.g., phenelzine, and tranylcypromine).
Note that antidepressants are acceptable as long as the subject has remained on them
at a stable dose for over 60 days prior to Screening and plans to remain on them
through the study;
15. Any malignant disease (other than basal cell carcinoma of the skin) with evidence of
disease within the past 5 years and with the potential for recurrence
Part 2:
Inclusion criteria:
1. Subject has completed part 1 of the study.
2. Subject projected not to need dopaminergic treatment except for treatment with
Monoamine Oxidase B (MAOB) inhibitors. MAOB inhibitors will be allowed if the patient
was already taking the same during part 1 of the study.
3. Subject has received K0706/placebo, as appropriate, within 4 weeks prior to end of
part 1 of the study.
4. Male subjects enrolled in the study should not father a child and are advised to
prevent the passage of semen to their sexual partner during intercourse using an
effective method, as judged by the Investigator, for the duration of the study and for
3 months after the last dose of study drug
Exclusion criteria:
1. Clinically significant or unstable psychiatric or medical condition, vital sign, or
laboratory abnormality that in the opinion of the investigator interferes with
participation in the study
2. Any condition that in the opinion of the Investigator represents an obstacle for study
conduct and/or represents a potential unacceptable risk for the subject.
3. Subject has any concurrent medical condition or uncontrolled, clinically significant
systemic disease (e.g., renal failure, heart failure, hypertension, liver disease,
diabetes, or anemia) that, in the opinion of the Investigator, could cause continued
treatment to be detrimental to the subject
Early Parkinson Disease, Parkinson's disease, Other, Brain & Neurological
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
This phase III trial compares the effect of selumetinib versus the standard of care treatment
with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously
untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E
mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by
blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and
vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. The overall goal of
this study is to see if selumetinib works just as well as the standard treatment of CV for
patients with LGG. Another goal of this study is to compare the effects of selumetinib versus
CV in subjects with LGG to find out which is better. Additionally, this trial will also
examine if treatment with selumetinib improves the quality of life for subjects who take it.
Kenneth Desantes, M.D.
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04166409
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Hide eligibility criteria
Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG)
without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular
Screening Reviews performed on APEC14B1 (NCT02402244) and that has not been treated
with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously
diagnosed, and there is no required time frame between biopsy/surgery and treatment
initiation.
• Patients with residual tumor after resection or progressive tumor after initial
diagnosis (with or without surgery) who have not received treatment (chemotherapy
and/or radiation) are eligible
• Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
• Eligible histologies will include all tumors considered low-grade glioma or low-grade
astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO
classification of central nervous system (CNS) tumors with the exception of
subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGG are eligible
• 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 (performed within
7 days prior to enrollment):
• Age: Maximum Serum Creatinine (mg/dL)
• 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days
prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed
on study regardless of their total and indirect [unconjugated] bilirubin levels as
long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(performed within 7 days prior to enrollment). For the purpose of this study, the ULN
for SGPT is 45 U/L
• Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (performed within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within
4 weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications)
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of
enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts
for optic pathway tumors) and/or spine (depending on the site(s) of primary disease)
with and without contrast must be performed within 4 weeks prior to enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
• All patients have signed an appropriate consent form and Health Insurance Portability
and Accountability Act (HIPAA) authorization form (if applicable)
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by
enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same
day to complete the Rapid Central Review
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible.
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is not in
itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular pressure
(IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Supplementation with vitamin E greater than 100% of the daily recommended dose. Any
multivitamin containing vitamin E must be stopped prior to study enrollment even if
less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy,
placement of a vascular access device or cerebral spinal fluid (CSF) diverting
procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
PROMMO Trial: Oral Misoprostol vs IV Oxytocin (PROMMO)
This is a prospective, randomized trial looking at the ideal method of labor induction for
women with prelabor rupture of membranes and an unfavorable cervical Bishop score. The study
will compare oral misoprostol and intravenous oxytocin.
Jacquelyn Adams
Female
18 Years and over
Early Phase 1
This study is also accepting healthy volunteers
NCT04478942
Show full eligibility criteria
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Inclusion Criteria:
• Early Term to late term pregnancy (>37 weeks and 0 days and <42 weeks and 0 days)
• Late Preterm Pregnancy (34 weeks and 0 days and <37 weeks)
• Confirmed rupture of membranes by either sterile speculum exam or AmniSure
• Simplified Bishop Score ≤ 6
• Maternal Age > 18 years old
• Singleton gestation
• Appropriate gestational age dating by certain LMP or ultrasound performed prior to 20
weeks gestational age
Exclusion Criteria:
• Concern for intra-amniotic infection
• Previous Cesarean delivery
• Lack of appropriate dating criteria for the pregnancy
• Inability to give informed consent in the patient's native language
• Known bleeding disorder such as von Willebrand's disease or hemophilia
• Anticoagulation administration within 24 hours of delivery
Premature Rupture of Membrane, Induction of Labor Affected Fetus / Newborn, Premature rupture of membranes, Other
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
This phase III trial studies if selumetinib works just as well as the standard treatment with
carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to
see if selumetinib is better than CV in improving vision in subjects with LGG of the optic
pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that
low-grade glioma tumor cells need for their growth. This results in killing tumor cells.
Drugs used as chemotherapy, such as carboplatin and vincristine, 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. It is not yet known whether selumetinib works better in
treating patients with NF1-associated low-grade glioma compared to standard therapy with
carboplatin and vincristine.
Kenneth Desantes, M.D.
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03871257
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or
germline genetic testing
• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that
has not been treated with any modality other than surgery
• For patients with optic pathway gliomas (OPGs):
• Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms
(including visual dysfunction, as defined below) or other exam findings
associated with the tumor
• Previously-diagnosed patients with OPG are eligible if they have new or worsening
neurologic symptoms (including visual dysfunction, as defined below) or have
tumor growth
• For both newly-diagnosed and previously-diagnosed OPG, the patient may be
eligible, irrespective of whether there has been tumor growth or other
neurological symptoms or worsening, if they meet at least one of the following
visual criteria:
• Visual worsening, defined as worsening of visual acuity (VA) or visual
fields (VF) documented within the past year (by examination or history); OR
• Significant visual dysfunction (defined as VA worse than normal for age by
0.6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
• For patients with LGG in other locations (i.e., not OPGs):
• Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms
or other exam findings associated with the tumor
• NOTE: Newly-diagnosed patients with LGG without associated neurologic
symptoms or exam findings are not eligible
• Previously-diagnosed patients with LGG are eligible if they have new or worsening
neurologic symptoms or have tumor growth
• Although not required, if a biopsy/tumor resection is performed, eligible histologies
will include all tumors considered LGG or low-grade astrocytoma (World Health
Organization [WHO] grade I and II) by 5th edition WHO classification of central
nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients must have two-dimensional measurable tumor >= 1 cm^2
• Patients with metastatic disease or multiple independent primary LGGs are allowed on
study
• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70
mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to
enrollment) as follows:
• Age; maximum serum creatinine (mg/dL)
• 2 to < 6 years; 0.8 (male) and 0.8 (female)
• 6 to < 10 years; 1 (male) and 1 (female)
• 10 to < 13 years; 1.2 (male) and 1.2 (female)
• 13 to < 16 years; 1.5 (male) and 1.4 (female)
• >= 16 years; 1.7 (male) and 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x
upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the
purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks
prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should have not
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment. Patients >= 18 years of age must
have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the
use of antihypertensive medications).
• Note: Adequate blood pressure can be achieved using medication for the treatment
of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site(s) of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• For patients who undergo a surgery on the target tumor (not required), a pre- and
post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine
(depending on the site(s) of primary disease) with and without contrast must also be
performed within 4 weeks prior to enrollment
• The post-operative MRIs should be performed ideally within 48 hours after surgery
if possible
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
• Patients must have receptive and expressive language skills in English or Spanish to
complete the quality of life (QOL) and neurocognitive assessments
• 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:
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/ condition, including
substance use disorders likely in the judgement of the investigator to interfere or
limit compliance with study requirements/treatment are not eligible
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Cardiac conditions:
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Ophthalmologic conditions:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Ophthalmological findings secondary to long-standing optic pathway glioma (such
as visual loss, optic nerve pallor, or strabismus) or longstanding
orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus)
will NOT be considered a significant abnormality for the purposes of the study
• Treatments and/or medications patient is receiving that would make her/him ineligible,
such as:
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
Any multivitamin containing vitamin E must be stopped prior to study enrollment
even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical
placement for vascular access or cerebrospinal fluid (CSF) diverting procedures
such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery prior to enrollment
• Patients who have an uncontrolled infection are not eligible
Brain and Nervous System, Brain/Central Nervous System, Low Grade Glioma, Neurofibromatosis Type 1, Visual Pathway Glioma
Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
This phase II trial studies how well the combination of dabrafenib and trametinib works after
radiation therapy in children and young adults with high grade glioma who have a genetic
change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells
and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells
by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their
growth. Giving dabrafenib with trametinib after radiation therapy may work better than
treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade
glioma.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03919071
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patients must be =< 25 years of age at the time
of enrollment on APEC14B1 Part A CNS/HGG pre-enrollment eligibility screening.
• Note: This required age range applies to the pre-enrollment eligibility screening
for all HGG patients. Individual treatment protocols may have different age
criteria.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient is suspected of having localized
newly-diagnosed HGG, excluding metastatic disease.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: Patient and/or their parents or legal guardians
have signed informed consent for eligibility screening on APEC14B1 Part A.
• PRE-ENROLLMENT ELIGIBILITY SCREENING: The specimens obtained at the time of diagnostic
biopsy or surgery must be submitted through APEC14B1 as soon as possible (ASAP),
preferably within 5 calendar days of the procedure.
• Please note: See the APEC14B1 Manual of Procedures for a full list of detailed
instructions for submitting required materials and for shipping details.
• Patients must be >= 3 years and =< 25 years of age at the time of enrollment.
• Patients must have eligibility confirmed by Rapid Central Pathology and Molecular
Screening Reviews performed on APEC14B1
• Newly diagnosed high-grade glioma with BRAF^V600-mutation
• Results for H3 K27M by immunohistochemistry (IHC) or sequencing
• Histologically confirmed high-grade glioma (World Health Organization [WHO] grade
III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic
pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG),
glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS).
• Patients must have had histologic verification of a high-grade glioma diagnosis. CSF
cytology by lumbar puncture must be done if clinically indicated and determined to be
safe prior to study enrollment. If cytology proves positive, the patient would be
considered to have metastatic disease and would, therefore, be ineligible.
• A pre- and post-operative brain MRI with and without contrast and a baseline spine MRI
with contrast must be obtained prior to enrollment. The requirement for a
post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is
positive, the patient would be considered to have metastatic disease and would be
ineligible.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age.
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment).
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment).
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to enrollment).
• 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 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
• Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
• Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
• Age 13 to < 16 years (Male 1.5 mg/dL, Female 1.4 mg/dL)
• Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment), and
• Serum glutamate pyruvate 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.
• Patients with a seizure disorder may be enrolled if their seizures are well controlled
while on non-enzyme inducing anticonvulsants permitted on this study.
• All patients and/or their parents or legal guardians must sign a written informed
consent
• Patients must be enrolled and protocol therapy must be projected to begin no later
than 31 days after definitive surgery (day 0). If a biopsy only was performed, the
biopsy date will be considered the date of definitive surgery. For patients who have a
biopsy or incomplete resection at diagnosis followed by additional surgery, the date
of the last resection will be considered the date of definitive surgery.
Exclusion Criteria:
• Patients with intrinsic brainstem or primary spinal cord tumors will be excluded.
• Patients with metastatic disease (defined as neuraxis dissemination either by imaging
or by cytology) will be excluded.
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the
treatment of HGG other than surgical intervention and/or corticosteroids.
• Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK
inhibitor, or an ERK inhibitor.
• Patients with a history of a malignancy with confirmed activating RAS mutation.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dabrafenib, trametinib, and their excipients.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease,
or uncontrolled infection), psychological, familial, sociological, or geographical
conditions that do not permit compliance with the protocol; or unwillingness or
inability to follow the procedures required in the protocol.
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel
or large bowel resection) that will interfere significantly with the absorption of
drugs.
• History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory
evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).
• History or current diagnosis of cardiac disease indicating significant risk of safety
for patients participating in the study such as uncontrolled or significant cardiac
disease, including any of the following:
• Recent myocardial infarction (within the last 6 months);
• Uncontrolled congestive heart failure;
• Unstable angina (within last 6 months);
• Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias
(e.g., sustained ventricular tachycardia, and clinically significant second or
third degree atrioventricular [AV] block without a pacemaker) except sinus
arrhythmia within the past 24 weeks prior to the first dose of study treatment;
• Coronary angioplasty or stenting (within last 6 months);
• Intra-cardiac defibrillators;
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
• Patients with a history or current evidence of retinal vein occlusion (RVO) or central
serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled
glaucoma or ocular hypertension).
• Patients with presence of interstitial lung disease or pneumonitis.
• Female patients who are pregnant are ineligible since there is yet no available
information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants for the duration of the study and for 4 months following discontinuation of
study therapy.
• Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained.
• Sexually active patients of reproductive potential (male or female) are not eligible
unless they have agreed to use an effective contraceptive method for the duration of
their study participation and for 4 months following discontinuation of study therapy.
Male patients (including those who have had a vasectomy) taking dabrafenib and
trametinib combination therapy must use a condom during intercourse while on study and
for 16 weeks after stopping treatment, and should not father a child during these
periods. Women of childbearing potential should use effective non-hormonal
contraception during therapy and for 4 weeks following discontinuation of dabrafenib
and at least 4 months following the last dose of trametinib in patients taking
combination therapy. Women should be advised that dabrafenib may decrease the efficacy
of hormonal contraceptives and an alternate method of contraception, such as barrier
methods, should be used.
Anaplastic Astrocytoma, Anaplastic Astrocytoma, Not Otherwise Specified, Anaplastic Ganglioglioma, Anaplastic Pleomorphic Xanthoastrocytoma, Glioblastoma, Malignant Glioma, WHO Grade 3 Glioma, Brain and Nervous System, Brain/Central Nervous System
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