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Use of High-resolution Manometry to Detect Upper Airway Obstruction During Sleep
Obstructive sleep apnea (OSA) is a major public health issue in both children and adults,
present in 1-5% of children and 10-30% of adults. It is characterized by repeated episodes of
airway obstruction during sleep, leading to brain arousal, sympathetic activation, oxygen
desaturation, sleep fragmentation, and non-restorative sleep. Patients report daytime
tiredness, insomnia, and morning headaches. Children with OSA experience daytime somnolence,
difficulties at school, behavioral problems, enuresis, and reduced quality of life. If left
untreated, OSA can lead to numerous complications including hypertension, cardiovascular
disease, stroke, and insulin resistance. Sleep partners are also affected, with patients
viewing their disorder as a burden and sleeping in separate rooms. Further, disease
prevalence is increasing as obesity increases.
Continuous positive airway pressure (CPAP) is the current gold standard treatment for OSA. If
used effectively and consistently, it can improve patient symptoms. However, adherence is
generally poor, with patients experiencing physical discomfort, chest discomfort, and dry
mouth. For those patients that cannot tolerate CPAP, surgical intervention is an option. In
children, this typically starts with adenotonsillectomy. However, 20-75% of children will
have persistent symptoms after adenotonsillectomy. In adults, anatomic factors including
tonsil hypertrophy and redundant pharyngeal tissue can contribute to upper airway obstruction
and may also necessitate higher pressures for effective CPAP treatment. Even if surgical
intervention does not cure the OSA, it may make CPAP more tolerable and improve CPAP
adherence.
Sleep-related airway obstruction is a complex phenomenon potentially involving multiple
anatomic levels. For patients with persistent symptoms despite initial therapy or intolerance
to CPAP, further evaluation of the upper airway is clinically valuable. Polysomnography (PSG)
is the gold standard for diagnosing OSA, but it does not provide information on the
location(s) of upper airway obstruction. Knowledge of the precise sites of obstruction is
critical to planning effective sleep surgery. Currently, this is accomplished with
drug-induced sleep endoscopy (DISE). DISE was originally proposed in 1991 and involves
administering anesthetic to a patient to simulate a sleep state, and then visualizing the
upper airway using transnasal flexible endoscopy. Sites of obstruction at key locations
including the adenoids, soft palate, lateral oropharynx, tongue base, and epiglottis can be
identified.
Though DISE offers valuable clinical information, it has notable limitations. First, it
cannot evaluate the entire upper airway simultaneously, as any obstruction occurring
superiorly precludes visualization of any obstruction occurring more inferiorly. Second,
interpretation of DISE is subjective and there is no universally accepted system for
analysis. Rating systems are qualitative, using grades such as complete, partial, or no
obstruction as opposed to quantitative measurements.
The optimal sleep assessment would be quantitative, reliable, and provide information on the
entire upper airway simultaneously. A potential alternative to DISE which could meet these
criteria is sleep manometry. Measurement of upper airway pressures captures the effects of
obstruction along the entire upper airway, from the nasopharynx to larynx. Prior studies have
attempted to employ manometry, but have been limited primarily by inadequate equipment and
suboptimal methods of data analysis. Woodson et al. used a solid-state manometer with
diameter of 2.3 mm and 5 sensors to detect palatal obstruction and tongue base obstruction in
patients with OSA. They also used the same approach to detect persistent tongue base
obstruction following uvulopalatopharyngoplasty. While these studies help demonstrate that
manometry can be a useful adjunct to OSA assessment, they are severely limited both by the
type of manometer used as well as the lack of a clear, detailed description of the method of
data analysis.
High-resolution manometry (HRM) uses pressure censors spaced 1 cm apart to allow for pressure
measurement along the entire upper airway. The investigators have previously applied HRM to
assessment of swallow physiology. Sophisticated methods of automated data analysis have been
developed that have been shown to be reliable for both expert and novice users . Further,
pattern recognition techniques have been applied to identify dysphagia and specific
swallowing abnormalities. Application of this technology and modification of existing data
analysis platforms will allow for a quantitative, reliable, and comprehensive assessment of
upper airway obstruction during sleep in both children and adults, with potential for
development of algorithms to predict effects of targeted surgical therapy at all levels of
the upper airway.
Timothy Mcculloch, MD
All
5 Years to 90 Years old
NA
This study is also accepting healthy volunteers
NCT04139499
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Inclusion Criteria:
ADULTS
• Age 18-90
• Any participant undergoing sleep endoscopy as part of standard clinical care would be
eligible. This entails physician concern for sleep-disordered breathing and
corresponding questionnaire and/or polysomnogram results supporting a diagnosis of
obstructive sleep apnea.
• Participants without apnea are eligible, provided they are undergoing tonsillectomy or
bronchoscopy for either chronic tonsillitis or airway assessment without concern for
history of sleep apnea.
• Women with childbearing potential will not be excluded, as the proposed experiment
would have no potential ramifications on childbearing potential.
CHILDREN
• Age 5-17
• Any patients undergoing sleep endoscopy as part of standard clinical care would be
eligible.
• Participants undergoing either tonsillectomy for chronic tonsillitis or bronchoscopy
for airway assessment.
• Women with childbearing potential will not be excluded, as the proposed experiment
would have no potential ramifications on childbearing potential.
Exclusion Criteria:
• Participant desire to avoid added anesthesia time.
• Inability to safely tolerate the added anesthesia time (about 5-10 minutes) for the
experiment (as judged by either otolaryngologist or anesthesiologist).
• Pregnant women
• Vulnerable groups (i.e., prisoners, individuals lacking consent capacity, individuals
unable to read the consent form).
Acute obstructive laryngitis [croup] and epiglottitis, Other, Obstructive Sleep Apnea
Treatment of Cytomegalovirus (CMV) Infections With Viral-Specific T Cells
The present trial will consist of the treatment of 20 pediatric and adult Hematopoietic Stem
Cell Transplantation (HSCT) recipients or immunocompromised participants diagnosed with
opportunistic Cytomegalovirus (CMV) infections with virus-specific, antigen-selected T-cells.
CMV-specific T-cells will be isolated from donor leukapheresis products using the CliniMACS®
Prodigy. Prior studies on transfer of CMV specific T-cells have been shown to be safe and
efficacious in the treatment of CMV infections.
The main trial objective is to evaluate the feasibility and safety of CMV-specific T-cell
transfer in adult and pediatric participants suffering from CMV infections or reactivation
following HSCT or due to other immunocompromised states (e.g.; primary immunodeficiency,
cytotoxic therapy).
Participants will be followed for one year.
Christian Capitini, MD
All
1 Month and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03798301
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Inclusion Criteria:
1. Adult or pediatric patient suffering from CMV reactivation/infections following HSCT
or due to other immunocompromised states (e.g.; primary immunodeficiency, cytotoxic
therapy).
• CMV reactivation/viremia defined as positive (>500 copies/ml) CMV qPCR and/or
• Presence of symptoms secondary to CMV infection or evidence of invasive CMV
infection (e.g. pneumonitis, colitis) AND
• Patients must have ONE OF THE FOLLOWING CRITERIA:
• Absence of an improvement of viral load after ≥ 14 days of antiviral therapy
with ganciclovir, valganciclovir or foscarnet (decrease by at least 1 log,
i.e. 10-fold), or
• New, persistent and/or worsening CMV-related symptoms, signs and/or markers
of end organ compromise while on antiviral therapy with ganciclovir,
valganciclovir or foscarnet, or
• Have contraindications or experience adverse effects of antiviral therapy
with ganciclovir, valganciclovir or foscarnet, or
• Known resistance to ganciclovir and/or foscarnet based on molecular testing.
2. Recipients of an allogeneic HSCT must be 28 days after stem cell infusion at the time
of T-cell transfer.
3. Written informed consent given by patient or legal representative.
4. Minimum patient age 1 month.
5. Minimum weight 7 lbs.
6. Female patients of childbearing age with negative pregnancy tests.
7. Patient Karnofsky/Lansky Performance Status >30%.
8. Donor eligible based on FACT infectious screening requirements.
Exclusion Criteria:
1. Patient with acute GVHD > grade 2 or active moderate or severe chronic GVHD at time of
T-cell transfer
2. Patient receiving steroids (>1.0 mg/kg body weight (BW) prednisone equivalent) at the
time of T-cell transfer
3. Patient received allogeneic HSCT less than 28 days prior to T-cell transfer
4. Patient treated with donor lymphocyte infusion (DLI) within 28 days prior to T-cell
transfer
5. Patient treated with Thymoglobulin (ATG), Alemtuzumab or T-cell immunosuppressive
monoclonal antibodies within 28 days.
6. Patient with organ dysfunction or failure as determined by Karnofsky (patients >16
years) or Lansky (patients ≤16 years) score ≤30% (Appendix 5)
7. Patients with CMV retinitis
8. Concomitant enrollment in another clinical trial with endpoints interfering with this
study
9. Any medical condition which could compromise participation in the study according to
the investigator's assessment
10. Known HIV infection
11. Female patient who is pregnant or breast-feeding, or adult of reproductive potential
not willing to use an effective method of birth control during study treatment. Note:
Women of childbearing potential must have a negative serum pregnancy test at study
entry.
12. Patients unwilling or unable to comply with the protocol or unable to give informed
consent.
Donor Eligibility:
The original donor will be the first choice as source of T cells. If the original donor is
not available for donation (such as NMDP donor, cord blood unit, or related donor not
available) of peripheral mononuclear cells or does not meet all donor eligibility criteria
(including donor selection criteria based on University of Wisconsin •Madison Standard
Operating Procedures for the selection of allogeneic donors), alternative related donors
will be selected, with preference for those who have full HLA matching in 6/6 loci over
those with partial HLA matching (≥ 3/6 HLA loci).
1. All donors must be ≥ 18 years old, available, CMV IgG positive, eligible and capable
of undergoing a single standard 2 blood volume leukapheresis. If original HSCT donor
is not available, CMV IgG negative or ineligible, a CMV IgG positive fully matched or
haploidentical family donor will be used.
2. Related donors must be at least partially HLA compatible, matching with recipient in
at least 3/6 HLA loci (HLA-A, HLA-B and HLA-DRB1 will be considered for this).
3. Donors must be CMV IgG seropositive.
4. Donors must show CMV T-cell activation after incubation with MACS GMP PepTivator
Peptide Pools of CMV pp65 before undergoing leukapheresis.
5. Donor must meet the criteria for donor selection defined in the Standard Operating
Procedures of the University of Wisconsin Hospitals and Clinics Stem Cell Transplant
Program and in FACT standards.
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
This phase I trial studies the safety of transplantation with a haploidentical donor
peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with
the immunomodulating drug, Zoledronate, given in the post-transplant period to treat
pediatric patients with relapsed or refractory hematologic malignancies or high risk solid
tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
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Inclusion Criteria:
• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
• Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation;
and
• The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi •EIA (Chagas)
Exclusion Criteria:
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Ill-Defined Sites, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma
Childhood Allergy and the Neonatal Environment (CANOE)
The purpose of this research study is to study the relationship between childhood asthma,
allergies, and early-life environmental factors that may cause childhood asthma and
allergies. Previous birth cohort studies have found early-life environmental factors such as
allergies, pollutants, viruses and bacteria have all contributed to the development of asthma
and allergies. Investigators are doing this research because there continues to be a strong
need to understand the root causes of asthma and allergies. The CANOE study is an
observational cohort study, which means investigators are not asking participants or
participant's child to change their medications and investigators will not be giving
participants or participant's child a study drug.
Anne Singh
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT04215783
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Inclusion Criteria:
1. History of or concurrent asthma or allergic rhinitis (hay fever) in either biologic
parent or sibling (at least one shared biological parent) by parental report. The
presence of paternal or sibling allergy or asthma will be ascertained by maternal
report.
2. Maternal age greater than or equal to 18 years at the time of study enrollment.
Exclusion Criteria:
1. Maternal HIV infection at time of delivery.
2. Plans for the family to move out of the geographic area during the period of the
study.
3. Does not speak English.
4. Current maternal use of progesterone during pregnancy to prevent preterm birth.
• Progesterone use is only an exclusion if currently being taken at time of
enrollment for preterm birth. Previous use to prevent preterm birth or use at any
time for other indications is allowed.
5. Pregnancy is a result of an embryo donor (egg and sperm donor pregnancies are
permitted).
6. Past or current medical problems or findings from physical examination or laboratory
testing which, in the opinion of the investigator or designee, may pose additional
risks from participation in the study, may interfere with the participant's ability to
comply with study requirements or that may impact the quality or interpretation of the
data obtained from the study.
Asthma in Children, Allergy, Allergic rhinitis due to animal (cat) (dog) hair and dander, Allergic rhinitis due to food, Allergic rhinitis due to pollen, Asthma, Other, Infections, Immune System & Allergies
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)
The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or
refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain
tumors for which there are no standard treatment options with curative potential.
Nicholas Pytel, DO
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g.,
neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain
tumors that are clinically or radiographically suspected to be relapsed, refractory,
or recurrent for which there are no standard treatment options with curative
potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll
without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky
performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to
study registration, and, unless deemed medically necessary, no transfusions are
allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study
registration, and, unless deemed medically necessary, no transfusions are allowed
between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60
ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at
least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have
availability or ability to collect an autologous hematopoietic stem cell back-up
product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+
cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the
initiative and means to be compliant with the protocol.
Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a
lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron
emission tomography (PET) positive may be enrolled at the investigator's discretion,
even if not associated with a measurable lesion of at least 10 mm. Patients with
neuroblastoma who have detectable disease may enroll provided they meet the
requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic
treatments for brain metastases prior to enrollment; by investigator assessment be
considered stable with no new signs or symptoms for at least 1 month, and on a stable
dose of steroids (unchanged for three weeks prior to registration or on a steroid
tapering regimen).
Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging
sequence.
• Patients with previously known neurological deficits must be clinically stable at time
of enrollment and able to complete all study related procedures. Patients with
documented or newly diagnosed neurological deficits will be enrolled at the
investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable
(unchanged for three weeks prior to registration) or on a steroid tapering regimen.
Initiation of steroids per routine care immediately prior to CLR 131 dosing is
acceptable.
Exclusion Criteria:
• Patients receiving active treatment for central nervous system metastases or those
that are likely to require active treatment during anticipated participation in this
trial. Patients with stable brain metastases treated with steroids may enroll at the
investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless
previously treated with surgery, systemic therapy, or radiotherapy with the patient
neurologically stable. Patients with metastatic brain tumors that have been previously
treated are allowed, provided the patient is neurologically stable (determined at the
investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain
types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to
skull-based metastases is not considered craniospinal radiation for the purposes of
this study]), at least 3 months must have elapsed. No washout is required for
palliative focal radiation. NOTE: Patients participating in non-interventional
clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a
cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in
this trial, are not eligible.
Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
This is a long-term follow-up safety and efficacy study of participants in clinical trials
for spinal muscular atrophy (SMA) who were treated with onasemnogene abeparvovec-xioi.
Participants will roll over from their respective previous (parent) study into this long-term
study for continuous monitoring of safety as well as monitoring of continued efficacy and
durability of response to onasemnogene abeparvovec-xioi treatment.
Jennifer Kwon, MD
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT04042025
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Inclusion Criteria:
• Any participant with SMA who received onasemnogene abeparvovec-xioi gene replacement
therapy in a Novartis Gene Therapies-sponsored clinical study
• Participant/parent/legal guardian willing and able to complete the informed consent
process and comply with study procedures and visit schedule
Exclusion Criteria:
• Parent/legal guardian unable or unwilling to participate in the long-term follow-up
safety study
Spinal Muscular Atrophy Type I, Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III, SMA, Spinal muscular atrophy, Other, Congenital & Chromosomal Abnormalities
The APOLLO study is being done in an attempt to improve outcomes after kidney transplantation
and to improve the safety of living kidney donation based upon variation in the
apolipoprotein L1 gene (APOL1). Genes control what is inherited from a family, such as eye
color or blood type. Variation in APOL1 can cause kidney disease. African Americans,
Afro-Caribbeans, Hispanic Blacks, and Africans are more likely to have the APOL1 gene
variants that cause kidney disease. APOLLO will test DNA from kidney donors and recipients of
kidney transplants for APOL1 to determine effects on kidney transplant-related outcomes.
Brad Astor, PhD, MPH
All
0 Years and over
NA
This study is NOT accepting healthy volunteers
NCT03615235
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Inclusion Criteria for Living Donors:
• Living kidney donors with self-reported recent African ancestry (defined as African
American, Afro-Caribbean, Hispanic black or African) will be eligible for inclusion.
Exclusion Criteria for Living Donors:
• Participants who are unable or unwilling to provide informed consent.
Enrollment and bio sample collection from deceased donors at OPOs ended on May 31, 2023 and
recruiting kidney transplant recipients ended on June 15, 2023.
Phase II started on 9/1/2023 and only Living Donors will be recruited for an additional 2
years.
Kidney Diseases, Kidney Failure, Kidney Disease, Chronic, Other
The mission of the SARP is to improve the understanding of severe asthma through integrated
study of its clinical and biological features and to evaluate their changes over time. The
ultimate goal of these efforts is to promote better treatments for severe asthma.
Loren Denlinger, MD, PhD
All
6 Years and over
N/A
This study is also accepting healthy volunteers
NCT01606826
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Asthmatic Patients:
Inclusion Criteria:
1. Physician diagnosis of asthma,
2. Age 6 years and older
3. Evidence of historical reversibility, including either:
• FEV1 bronchodilator reversibility ≥ 12%, or
• Airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL.
Exclusion Criteria:
1. Pregnancy during the characterization phase,
2. Current smoking,
3. Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years
if <30 years of age (Note: if a subject has a smoking history, no smoking within the
past year),
4. Other chronic pulmonary disorders associated with asthma-like symptoms, including (but
not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic
bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and
at the PI's discretion), severe scoliosis or chest wall deformities that affect lung
function, or congenital disorders of the lungs or airways,
5. History of premature birth before 35 weeks gestation,
6. Unwillingness to receive an intramuscular triamcinolone acetonide injection,
7. Evidence that the participant or family may be unreliable or poorly adherent to their
asthma treatment or study procedures,
8. Planning to relocate from the clinical center area before study completion,
9. Any other criteria that place the subject at unnecessary risk according to the
judgment of the Principal Investigator and/or attending physician(s) of record, or
10. Currently participating in an investigational drug trial for asthma therapies.
Healthy Controls:
Inclusion criteria: Healthy subjects between the age of 18 and 65 years. Exclusion criteria
1. History of chronic diseases that affect the lungs,
2. A history suggestive of allergic rhinitis, eczema or chronic sinusitis,
3. An improvement in FEV1 of more than 12% following 4 puffs of albuterol,
4. Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years
if <30 years of age, or any smoking within the past year,
5. Respiratory tract infection within the past 4 weeks,
6. Pregnancy,
7. History of premature birth (<35 weeks).
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to
children by their health care provider, act in the bodies of children and young adults in
hopes to find the most safe and effective dose for children. The primary objective of this
study is to evaluate the PK of understudied drugs currently being administered to children
per SOC as prescribed by their treating provider.
Maria Stanley
All
0 Years to 20 Years old
NA
This study is also accepting healthy volunteers
NCT04278404
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Inclusion Criteria:
1. Participant is < 21 years of age
2. Parent/ Legal Guardian/ Adult Participant can understand the consent process and is
willing to provide informed consent/HIPAA:
3. (a) Participant is receiving one or more of the study drugs of interest at the time of
enrollment or (b) Participant is NOT receiving one or more of the study drugs of
interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
1. Participant has a known pregnancy
Below exclusion criteria apply only to:
Participants receiving one or more of the study drugs of interest at the time of
enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for
details on enrollment cohort specifications and additional eligibility criteria)
2. Has had intermittent dialysis within previous 24 hours
3. Has had a kidney transplant within previous 30 days
4. Has had a liver transplant within previous 1 year
5. Has had a stem cell transplant within previous 1 year
6. Has had therapeutic hypothermia within previous 24 hours
7. Has had plasmapheresis within the previous 24 hours
8. Has a Ventricular Assist Device
9. Has any condition which would make the participant, in the opinion of the
investigator, unsuitable for the study
Coronavirus Infection (COVID-19), Pulmonary Arterial Hypertension, Urinary Tract Infections in Children, Hypertension, Pain, Hyperphosphatemia, Primary Hyperaldosteronism, Edema, Hypokalemia, Heart Failure, Hemophilia, Menorrhagia, Insomnia, Pneumonia, Skin Infection, Arrythmia, Asthma in Children, Bronchopulmonary Dysplasia, Adrenal Insufficiency, Fibrinolysis, Hemorrhage, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder, Down Syndrome, Other
Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA)
Spinal muscular atrophy (SMA) is a neurogenetic disorder caused by a loss or mutation in the
survival motor neuron 1 gene (SMN1) on chromosome 5q13, which leads to reduced SMN protein
levels and a selective dysfunction of motor neurons. SMA is an autosomal recessive, early
childhood disease with an incidence of 1:10,000 live births. SMA is the leading cause of
infant mortality due to genetic diseases.
Until recently, the mainstay of treatment for these patients was supportive medical care.
However, advances in medical treatment focusing on gene replacement, gene enhancement, motor
neuron protection and muscle enhancement is likely to change the management and prognosis of
these patients in the future.
The purpose of this registry is to assess the long term outcomes of patients with SMA in the
context of advances in treatment options.
Jennifer Kwon, MD
All
Not specified
NA
This study is NOT accepting healthy volunteers
NCT04174157
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Inclusion Criteria:
• Patients with SMA, genetically confirmed on or after 24 May 2018.
• Appropriate consent/assent has been obtained for participation in the registry
Exclusion Criteria:
•Currently enrolled in an interventional clinical trial involving an investigational
medicinal product to treat SMA.
Note: Patients that are participating in a Compassionate Use Program (CUP) for AVXS-101
(Zolgensma) such as a Managed Access Program (MAP), an Expanded Access Program (EAP),
Single Patient Investigational New Drug (IND) (SPI) or Named Patient Program (NPP) are
eligible to enroll in the registry regardless of the date of genetic confirmation of SMA.
Spinal Muscular Atrophy (SMA), Spinal muscular atrophy, Other
Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all
pediatric and adult participants exposed to Gene-modified (GM) T cell therapy participating
in a previous Celgene sponsored or Celgene alliance partner sponsored study.
Participants who received at least one GM T cell infusion will be asked to enroll in this
LTFU protocol upon either premature discontinuation from, or completion of the prior parent
treatment protocol.
Natalie Callander, MD
All
Not specified
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03435796
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Inclusion Criteria:
• Received at least one gene-modified (GM) T-cell infusion in a previous Celgene
sponsored or Celgene alliance partner-sponsored study, and have discontinued, or
completed the post-treatment follow-up period in the parent treatment protocol, as
applicable.
• Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form
prior to any study-related assessments/procedures being conducted.
Exclusion Criteria:
Not Applicable
Other protocol-defined inclusion/exclusion criteria apply
CHaractErizing CFTR Modulated Changes in Sweat Chloride and Their Association With Clinical Outcomes (CHEC-SC)
This is a multicenter, cross-sectional, cohort study which will collect contemporary sweat
chloride (SC) values from approximately 5000 Cystic Fibrosis (CF) patients prescribed and
currently receiving commercially approved Cystic Fibrosis transmembrane conductance regulator
(CFTR) modulator therapies.
Hara Levy, MD
All
4 Months and over
NA
This study is NOT accepting healthy volunteers
NCT03350828
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Inclusion Criteria:
1. Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative
2. Enrolled in the CFFPR
3. Male or female ≥ 4 months of age on day of study visit
4. Diagnosis of CF.
5. Current treatment with a prescribed commercially approved CFTR modulator for at least
90 days prior to enrollment
6. Able to perform the testing and procedures required for this study, as judged by the
investigator
Additional Inclusion Criteria for CHEC-PKPD Sub-Study:
1. Male or female ≥ 6 years of age on day of study visit.
2. Current treatment with elexacaftor/tezacaftor/ivacaftor for at least 90 days prior to
enrollment.
3. Last dose of elexacaftor/tezacaftor/ivacaftor taken at least 24hours and last dose of
ivacaftor taken at least 12 hours prior to trough blood draw on day of visit.
Exclusion Criteria:
1. Presence of a condition or abnormality that, in the opinion of the Investigator, would
compromise the safety of the patient or the quality of the data
2. Currently enrolled in an investigational trial (including open-label follow-on studies
and Early Access Programs (EAP) of an agent expected to have an impact on sweat
chloride (refer to current list provided on study website)
Cystic Fibrosis, Respiration Disorders [C08], Other
This trial is a randomized, double-blind, placebo controlled trial designed to test whether
two years treatment of preschool children aged 2-3 years of age at high risk for asthma with
omalizumab (anti-IgE) for two years will prevent the progression to childhood asthma, as
reflected by a reduction in the prevalence of active asthma in the Final 12 months during 2
year observation period off study drug.
Daniel Jackson
All
24 Months to 47 Months old
Phase 2
This study is NOT accepting healthy volunteers
NCT02570984
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Inclusion Criteria:
1. Parent/guardian must be able to understand and provide signed and dated written
informed consent; he/she must also be able to communicate with study staff.
2. 24-47 months of age at randomization
3. 2-4 wheezing episodes in the past year
4. positive allergy to aeroallergen
5. first degree relative with history or current diagnosis of asthma or allergy
6. If is participating in a food immunotherapy treatment that is not part of a clinical
trial, has been on an established maintenance regimen implemented continuously for a
minimum of 2 months.
Exclusion Criteria:
1. >4 episodes of wheezing in the past year
2. Use of Step 5 or Step 6 therapy (ICS plus LABA ) at the time of enrollment (Visit 0).
3. Need for systemic corticosteroids or a hospitalization for respiratory symptoms within
four weeks prior to screening.
4. Three or more courses of systemic corticosteroids for wheezing illnesses in the last
year
5. More than four days of symptoms of wheezing, or tightness in the chest or cough in the
past two weeks causing at least minimal limitation of activity
6. More than four days of albuterol treatment (for symptoms) in the past two weeks
7. More than one night of symptoms of wheezing, or tightness in the chest or cough
causing sleep disruption in the past two weeks
8. More than one night of albuterol treatment (for symptoms) in the past two weeks
9. Prematurity (<34 weeks gestation)
10. Need for oxygen for more than 5 days in the neonatal period
11. History of intubation or mechanical ventilation for respiratory illness
12. Other significant medical conditions, including: major congenital anomalies, cystic
fibrosis, chronic pulmonary diseases, bronchopulmonary dysplasia, thoracic surgery,
history of tuberculosis, immunodeficiency (primary or secondary), seizure disorders
13. Expecting to relocate within 4 years of study initiation to a place which would make
in-person clinical visits impossible
14. Deemed unable to adhere to study activities
15. Prior aeroallergen immunotherapy or use of biologics including anti-IgE
16. Prior IVIG or systemic immunosuppressant other than corticosteroids
17. History of hypoxic seizures during a wheezing episode
18. Total IgE outside of the omalizumab dosing range.
19. Enrolled in any clinical medication trial within the past 30 days.
20. With platelet counts < 150 x 109/L at the Screening Visit (V0)
21. Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator, may pose
additional risks from participation in the study, may interfere with the participant's
ability to comply with study requirements or may impact the quality or interpretation
of the data obtained from the study.
22. History of severe anaphylactic/anaphylactoid reactions from any cause
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction
chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial will also study the outcomes of patients with mixed phenotype acute
leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk
ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
Induction and Consolidation. This part will collect information on the leukemia, as well as
the effects of the initial treatment, to classify patients into post-consolidation treatment
groups. On the second part of this study, patients with HR B-ALL will receive the remainder
of the chemotherapy cycles (interim maintenance I, delayed intensification, interim
maintenance II, maintenance), with some patients randomized to receive inotuzumab. The
patients that receive inotuzumab will not receive part of delayed intensification. Other aims
of this study include investigating whether treating both males and females with the same
duration of chemotherapy maintains outcomes for males who have previously been treated for an
additional year compared to girls, as well as to evaluate the best ways to help patients
adhere to oral chemotherapy regimens. Finally, this study will be the first to track the
outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed
Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Cathy Lee-Miller, MD
All
1 Year to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03959085
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Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B-LLy patients may directly
enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on
central confirmatory testing to have B-ALL must meet the B-ALL criteria above
(age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL
stratum before the end of induction.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• Central nervous system (CNS) status must be determined prior to enrollment based on a
sample obtained prior to administration of any systemic or intrathecal chemotherapy,
except for steroid pretreatment and cytoreduction. It is recommended that intrathecal
cytarabine be administered at the time of the diagnostic lumbar puncture. This is
usually done at the time of the diagnostic bone marrow or venous line placement to
avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic
chemotherapy must begin within 72 hours of this intrathecal therapy.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment and steroid cytoreduction or the
administration of intrathecal cytarabine, patients must not have received any prior
cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any
cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of
systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
The investigators want to study if lower doses of chemotherapy will help babies with SCID to
achieve good immunity with less short and long-term risks of complications after
transplantation. This trial identifies babies with types of immune deficiencies that are most
likely to succeed with this approach and offers them transplant early in life before they get
severe infections or later if their infections are under control. It includes only patients
receiving unrelated or mismatched related donor transplants.
The study will test if patients receiving transplant using either a low dose busulfan or a
medium dose busulfan will have immune recovery of both T and B cells, measured by the ability
to respond to immunizations after transplant. The exact regimen depends on the subtype of
SCID the patient has. Donors used for transplant must be unrelated or half-matched related
(haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance
of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T
cells removed, using a newer, experimental approach of a well-established technology. Once
the stem cell transplant is completed, patients will be followed for 3 years. Approximately
9-18 months after the transplant, vaccinations will be administered, and a blood test
measuring whether your child's body has responded to the vaccine will be collected.
Christian Capitini, MD
All
0 Years to 2 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03619551
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Inclusion Criteria:
1. Infants with SCID, either typical or leaky or Omenn syndrome.
1. Typical SCID is defined as either of the following
• Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or
very low T cell function (<10% of lower limit of normal) as measured by response
to phytohemagglutinin OR
• Presence of maternally derived T cells
2. Leaky SCID is defined as the following
• Absence of maternally derived T cells
• AND either one or both of the following (i, ii): i) <50% of lower limit of normal T
cell function as measured by response to PHA OR <30% of lower limit of normal T cell
function as measured by response to CD3 ii) Absent or <10% of lower limit of normal
proliferative responses to candida and tetanus toxoid antigens (must document post
vaccination or exposure for this criterion to apply)
• AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter
ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of
age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+
or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
3. Omenn syndrome • Generalized skin rash
• Maternal lymphocytes tested for and not detected.
• >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of
age)
• Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to
antigens (Candida, tetanus) to which the patient has been exposed IF:
Proliferation to antigen was not performed, but at least 4 of the following 8
supportive criteria, at least one of which must be among those marked with an
asterisk (*) below are present, the patient is eligible as Omenn Syndrome.
1. Hepatomegaly
2. Splenomegaly
3. Lymphadenopathy
4. Elevated IgE
5. Elevated absolute eosinophil count
6. *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload
report)
7. *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or
SI < 30
8. *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells
below the lower level of normal
2. Documented mutation in one of the following SCID-related genes
a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1,
RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a
suitable donor and graft source
1. Haploidentical related mobilized peripheral blood cells
2. 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor
mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment
Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:
For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks
6. Adequate organ function defined as:
1. Cardiac:
Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥
26% by echocardiogram.
2. Hepatic:
Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have
been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and
ALT < 5.0 x ULN for age.
3. Renal:
GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated
GFR is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine
clearance or nuclear GFR, and must be > 50 mL/min/1.73 m2.
4. Pulmonary No need for supplemental oxygen and O2 saturation > 92% on room air at sea
level (with lower levels allowed at higher elevations per established center standard
of care).
Exclusion Criteria:
1. Presence of any serious life-threatening or opportunistic infection at time of
enrollment and prior to the initiation of the preparative regimen. Serious infections
as defined below that occur after enrollment must be reported immediately to the Study
Coordinating Center, and enrollment will be put on hold until the infection resolves.
Ideally enrolled subjects will not have had any infection. If patients have
experienced infections, these must have resolved by the following definitions:
a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site must be negative and patient has completed appropriate
course of antibacterial therapy (typically at least 10 days).
ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical
signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course
of antibacterial therapy (typically at least 10 days).
iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution
of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed
appropriate course of antibacterial therapy (typically at least 10 days). If possible,
radiographic resolution should also be demonstrated.
b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site is negative and patient has completed appropriate course of
antifungal therapy (typically at least 14 days). The patient may be continued on
antifungal prophylaxis following completion of the treatment course.
c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen
requirement, etc.) and patient has completed appropriate course of therapy (typically
at least 21 days). If possible, radiographic resolution should also be demonstrated.
The patient may be continued on prophylaxis following completion of the treatment
course.
d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must
be re-tested and are negative.
ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete
resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible,
radiographic resolution should also be demonstrated.
2. Patients with HIV or HTLV I/II infection will be excluded.
SCID, Other Hematopoietic, Unknown Sites, Hematologic cancers, other
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Margo Hoover-Regan
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213652
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Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the
presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment
with other ALK inhibitors is permitted given that at least 5 half-lives or 21
days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is
currently no available information regarding human fetal or teratogenic toxicities;
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment and for one week after the
last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the
end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Margo Hoover-Regan
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03155620
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects
with low risk germ cell tumors for recurrence after their tumor is removed. When the germ
cell tumor has spread outside of the organ in which it developed, it is considered
metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. The trial studies
whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic
standard risk germ cell tumors.
Margo Hoover-Regan
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT03067181
Show full eligibility criteria
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Inclusion Criteria:
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and
stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patients must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I
germ cell tumor; for the standard risk arms, patients must be newly diagnosed with
metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary
extracranial germ cell tumor in any of the categories outlined below is required of
all patients at enrollment except for those who were initially diagnosed with stage I
non-seminoma malignant GCT and later recur during observation post surgery off study;
for these patients, if elevated tumor markers rise to > 5 x upper limit of normal
(ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is
not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk
sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT);
tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage:
COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC)
testicular stage IA, IB and IS; histology: must contain at least one of the following:
yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular
stage IA IB, and IS; histology: may contain immature/mature teratoma; may NOT contain
yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) <
11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk;
histology: must contain at least one of the following: yolk sac tumor, embryonal
carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op:
alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age
(years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the
study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components
of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with
other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac
tumor is the only malignant component present, then it must be deemed by the
pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
(mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L) (within 7 days prior to enrollment)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to
enrollment) AND
• Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol
treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL
• Pure immature teratoma COG stage II •IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that
contraindicate the use of bleomycin are ineligible for the standard risk arms of the
trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Hodgkin's Lymphoma, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
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.
Cathy Lee-Miller, MD
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
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.
Margo Hoover-Regan
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.
Margo Hoover-Regan
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.
Cathy Lee-Miller, MD
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
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
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.
Nicholas Pytel, DO
All
2 Years to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04166409
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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
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.