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NCT03794349Active, not recruitingPhase 2

Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma

A Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab With or Without Eflornithine (DFMO) in Children With Relapsed, Refractory or Progressive Neuroblastoma

Source: ClinicalTrials.gov · Last updated 18 Feb 2026

Brief summary (registry, in English)

This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back (relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Eflornithine blocks the production of chemicals called polyamines that are important in the growth of cancer cells. Giving eflornithine with irinotecan hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with relapsed or refractory neuroblastoma.

Status (registry)
Active, not recruiting
Phase (registry)
Phase 2
Study type
Interventional
Enrollment
94 (actual)
First submitted
2 Jan 2019
Start date
8 Jul 2019
Primary completion date
31 Mar 2025
Lead sponsor
Children's Oncology Group
NCT number
NCT03794349

What you commit to

  • Study type: Interventional · Phase 2
  • Participants enrolled: 94
  • From 8 Jul 2019 to the primary completion date, 31 Mar 2025
  • 145 sites in 5 countries
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study. Based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential must have a negative pregnancy test to be eligible for this study.
  • Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
    • Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible.
  • Patients must not have received prior treatment with irinotecan and temozolomide.
  • Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible.
  • Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible.
  • Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not be eligible for this trial. Additionally, patients with significant malabsorption will not be eligible for this trial.

Other illness

  • Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
  • Patients with symptoms of congestive heart failure are not eligible.
  • Patients must not have uncontrolled infection.
  • Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
  • Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible.

Lab values

  • Patients with only elevated catecholamines (i.e. \> 2 x ULN) are NOT eligible for this study.

Other

  • Patients must not have \>= grade 2 diarrhea.

Who the study is looking for

  • Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e. \> 2 x upper limit of normal \[ULN\]), at the time of initial diagnosis.
  • For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound as intended to treat high-risk disease. The doses of chemotherapy must be comparable to those used in frontline high-risk neuroblastoma therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531). Patients must have ONE of the following:
    • First episode of recurrent high-risk disease following completion of aggressive multi-drug frontline high-risk therapy.
    • First episode of progressive high-risk disease during aggressive multi-drug frontline therapy.
    • Primary resistant/refractory disease (less than partial response by International Neuroblastoma Response Criteria \[INRC\]) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, etc.).
  • Patients must have at least ONE of the following at the time of enrollment:
    • Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as \>= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET) scan.
    • MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction.
    • Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma. Biopsy is not required for patients who have a new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy.
    • Patients with bone marrow disease only will be eligible if they have more than 5% disease involvement (documented neuroblastoma cells) in at least one sample from bilateral bone marrow biopsies.
    • Note: Patients with elevated catecholamines (i.e. \> 2 x ULN) only are NOT eligible for this study.
  • 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.
  • Primary refractory/resistant patients must have received at least 4 cycles of frontline high-risk chemotherapy. Frontline therapy may also have included surgery, chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy, radiotherapy, and retinoids but must NOT have received second line therapy for resistant/refractory, relapsed, or progressive disease. Patients who received intensified therapy for poor induction response or refractory disease (e.g. MIBG) will be considered to have received second line therapy and will not be eligible.
  • At least 14 days must have elapsed since completion of myelosuppressive therapy.
  • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count \[ANC\] 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.
  • No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions. However, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response. Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. Palliative radiation while on study is not permitted.
  • Patients are eligible \>= 6 weeks after autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following 131 I-MIBG therapy) as long as hematologic and other eligibility criteria have been met.
  • Patients are eligible \>= 6 weeks after therapeutic 131 I-MIBG provided that all other eligibility criteria are met.
  • Subjects who have previously received anti-GD2 monoclonal antibodies with or without retinoids for biologic therapy are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2 monoclonal antibodies in combination with chemotherapy.
  • Subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads are eligible.
  • Subjects who have previously received DFMO are eligible for this study provided they have not had progressive disease while receiving DFMO or progressed/relapsed within 3 months of completing DFMO.
  • Patients must not have received long-acting myeloid growth factors (e.g. pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor.
  • For patients with solid tumors (without marrow involvement) including status post SCT: peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment).
  • For patients with solid tumors (without marrow involvement) including status post SCT: platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
  • Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and transfusion independent platelet count criteria are met (as above). However, these patients are not evaluable for hematological toxicity.
  • Creatinine clearance or radioisotope GFR \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
    • 1 to \< 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
    • 2 to \< 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
    • 6 to \< 10 years (male 1 mg/dL, female 1 mg/dL)
    • 10 to \< 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
    • 13 to \< 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
    • \>= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
  • Total bilirubin =\< 1.5 x ULN for age (within 7 days prior to enrollment).
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5.0 x ULN for age (=\< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment).
  • Shortening fraction of \>= 27% by echocardiography (ECHO) (within 7 days prior to enrollment).
  • Ejection fraction of \>= 50% by ECHO or gated radionuclide study (within 7 days prior to enrollment).
  • No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry \> 94% if there is a clinical indication for pulse oximetry. Normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung for carbon monoxide \[DLCO)\] are required if there is a clinical indication for determination. For patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required.
  • Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
  • Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants.
  • CNS toxicity =\< grade 2.

Age in the registry: 1 year to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (145)

Sites in registry order. Save your city in your profile to sort them by distance.

SiteCityCountrySite status
John Hunter Children's Hospital
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Hunter Regional Mail CentreAustraliaUnknown status
Women's and Children's Hospital-Adelaide
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North AdelaideAustraliaUnknown status
Royal Children's Hospital
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ParkvilleAustraliaUnknown status
Perth Children's Hospital
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PerthAustraliaUnknown status
Sydney Children's Hospital
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RandwickAustraliaUnknown status
Queensland Children's Hospital
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South BrisbaneAustraliaUnknown status
The Children's Hospital at Westmead
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WestmeadAustraliaUnknown status
IWK Health Centre
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HalifaxCanadaUnknown status
McMaster Children's Hospital at Hamilton Health Sciences
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HamiltonCanadaUnknown status
Kingston Health Sciences Centre
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KingstonCanadaUnknown status
Children's Hospital
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LondonCanadaUnknown status
The Montreal Children's Hospital of the MUHC
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MontrealCanadaUnknown status
Centre Hospitalier Universitaire Sainte-Justine
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MontrealCanadaUnknown status
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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QuébecCanadaUnknown status
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
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SherbrookeCanadaUnknown status
Janeway Child Health Centre
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St. John'sCanadaUnknown status
Hospital for Sick Children
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TorontoCanadaUnknown status
CancerCare Manitoba
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WinnipegCanadaUnknown status
Christchurch Hospital
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ChristchurchNew ZealandUnknown status
Starship Children's Hospital
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GraftonNew ZealandUnknown status
HIMA San Pablo Oncologic Hospital
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CaguasPuerto RicoUnknown status
Children's Hospital Medical Center of Akron
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AkronUnited StatesUnknown status
Albany Medical Center
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AlbanyUnited StatesUnknown status
Lehigh Valley Hospital-Cedar Crest
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AllentownUnited StatesUnknown status
C S Mott Children's Hospital
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Ann ArborUnited StatesUnknown status
Children's Healthcare of Atlanta - Arthur M Blank Hospital
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AtlantaUnited StatesUnknown status
Children's Hospital Colorado
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AuroraUnited StatesUnknown status
Dell Children's Medical Center of Central Texas
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AustinUnited StatesUnknown status
University of Maryland/Greenebaum Cancer Center
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BaltimoreUnited StatesUnknown status
Johns Hopkins University/Sidney Kimmel Cancer Center
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BaltimoreUnited StatesUnknown status
Sinai Hospital of Baltimore
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BaltimoreUnited StatesUnknown status
Eastern Maine Medical Center
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BangorUnited StatesUnknown status
Children's Hospital of Alabama
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BirminghamUnited StatesUnknown status
Saint Luke's Cancer Institute - Boise
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BoiseUnited StatesUnknown status
Dana-Farber Cancer Institute
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BostonUnited StatesUnknown status
Roswell Park Cancer Institute
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BuffaloUnited StatesUnknown status
University of Vermont and State Agricultural College
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BurlingtonUnited StatesUnknown status
Carolinas Medical Center/Levine Cancer Institute
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CharlotteUnited StatesUnknown status
University of Virginia Cancer Center
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CharlottesvilleUnited StatesUnknown status
University of Illinois
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ChicagoUnited StatesUnknown status
University of Chicago Comprehensive Cancer Center
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ChicagoUnited StatesUnknown status
Lurie Children's Hospital-Chicago
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ChicagoUnited StatesUnknown status
Cincinnati Children's Hospital Medical Center
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CincinnatiUnited StatesUnknown status
Cleveland Clinic Foundation
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ClevelandUnited StatesUnknown status
Rainbow Babies and Childrens Hospital
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ClevelandUnited StatesUnknown status
Prisma Health Richland Hospital
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ColumbiaUnited StatesUnknown status
Nationwide Children's Hospital
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ColumbusUnited StatesUnknown status
Driscoll Children's Hospital
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Corpus ChristiUnited StatesUnknown status
UT Southwestern/Simmons Cancer Center-Dallas
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DallasUnited StatesUnknown status
Medical City Dallas Hospital
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DallasUnited StatesUnknown status
Dayton Children's Hospital
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DaytonUnited StatesUnknown status
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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DenverUnited StatesUnknown status
Blank Children's Hospital
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Des MoinesUnited StatesUnknown status
Wayne State University/Karmanos Cancer Institute
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DetroitUnited StatesUnknown status
Children's Hospital of Michigan
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DetroitUnited StatesUnknown status
Kaiser Permanente Downey Medical Center
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DowneyUnited StatesUnknown status
Duke University Medical Center
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DurhamUnited StatesUnknown status
Michigan State University
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East LansingUnited StatesUnknown status
Golisano Children's Hospital of Southwest Florida
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Fort MyersUnited StatesUnknown status
Cook Children's Medical Center
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Fort WorthUnited StatesUnknown status
University of Florida Health Science Center - Gainesville
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GainesvilleUnited StatesUnknown status
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
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Grand RapidsUnited StatesUnknown status
BI-LO Charities Children's Cancer Center
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GreenvilleUnited StatesUnknown status
Hackensack University Medical Center
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HackensackUnited StatesUnknown status
Connecticut Children's Medical Center
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HartfordUnited StatesUnknown status
Penn State Children's Hospital
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HersheyUnited StatesUnknown status
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
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HollywoodUnited StatesUnknown status
Kapiolani Medical Center for Women and Children
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HonoluluUnited StatesUnknown status
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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HoustonUnited StatesUnknown status
Ascension Saint Vincent Indianapolis Hospital
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IndianapolisUnited StatesUnknown status
Riley Hospital for Children
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IndianapolisUnited StatesUnknown status
University of Iowa/Holden Comprehensive Cancer Center
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Iowa CityUnited StatesUnknown status
University of Mississippi Medical Center
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JacksonUnited StatesUnknown status
Nemours Children's Clinic-Jacksonville
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JacksonvilleUnited StatesUnknown status
Bronson Methodist Hospital
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KalamazooUnited StatesUnknown status
Children's Mercy Hospitals and Clinics
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Kansas CityUnited StatesUnknown status
East Tennessee Childrens Hospital
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KnoxvilleUnited StatesUnknown status
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
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Las VegasUnited StatesUnknown status
Summerlin Hospital Medical Center
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Las VegasUnited StatesUnknown status
Sunrise Hospital and Medical Center
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Las VegasUnited StatesUnknown status
University Medical Center of Southern Nevada
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Las VegasUnited StatesUnknown status
University of Kentucky/Markey Cancer Center
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LexingtonUnited StatesUnknown status
Arkansas Children's Hospital
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Little RockUnited StatesUnknown status
Miller Children's and Women's Hospital Long Beach
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Long BeachUnited StatesUnknown status
Cedars-Sinai Medical Center
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Los AngelesUnited StatesUnknown status
Children's Hospital Los Angeles
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Los AngelesUnited StatesUnknown status
Norton Children's Hospital
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LouisvilleUnited StatesUnknown status
Valley Children's Hospital
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MaderaUnited StatesUnknown status
University of Wisconsin Carbone Cancer Center - University Hospital
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MadisonUnited StatesUnknown status
Loyola University Medical Center
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MaywoodUnited StatesUnknown status
Saint Jude Children's Research Hospital
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MemphisUnited StatesUnknown status
University of Miami Miller School of Medicine-Sylvester Cancer Center
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MiamiUnited StatesUnknown status
Nicklaus Children's Hospital
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MiamiUnited StatesUnknown status
Children's Hospital of Wisconsin
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MilwaukeeUnited StatesUnknown status
NYU Langone Hospital - Long Island
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MineolaUnited StatesUnknown status
University of Minnesota/Masonic Cancer Center
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MinneapolisUnited StatesUnknown status
Children's Hospitals and Clinics of Minnesota - Minneapolis
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MinneapolisUnited StatesUnknown status
West Virginia University Healthcare
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MorgantownUnited StatesUnknown status
Morristown Medical Center
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MorristownUnited StatesUnknown status
The Children's Hospital at TriStar Centennial
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NashvilleUnited StatesUnknown status
Vanderbilt University/Ingram Cancer Center
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NashvilleUnited StatesUnknown status
Yale University
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New HavenUnited StatesUnknown status
The Steven and Alexandra Cohen Children's Medical Center of New York
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New Hyde ParkUnited StatesUnknown status
Ochsner Medical Center Jefferson
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New OrleansUnited StatesUnknown status
Children's Hospital New Orleans
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New OrleansUnited StatesUnknown status
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New YorkUnited StatesUnknown status
Children's Hospital of The King's Daughters
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NorfolkUnited StatesUnknown status
Kaiser Permanente-Oakland
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OaklandUnited StatesUnknown status
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesUnknown status
Children's Hospital and Medical Center of Omaha
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OmahaUnited StatesUnknown status
University of Nebraska Medical Center
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OmahaUnited StatesUnknown status
Children's Hospital of Orange County
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OrangeUnited StatesUnknown status
Nemours Children's Hospital
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OrlandoUnited StatesUnknown status
Arnold Palmer Hospital for Children
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OrlandoUnited StatesUnknown status
Lucile Packard Children's Hospital Stanford University
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Palo AltoUnited StatesUnknown status
Saint Jude Midwest Affiliate
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PeoriaUnited StatesUnknown status
Children's Hospital of Philadelphia
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PhiladelphiaUnited StatesUnknown status
Children's Hospital of Pittsburgh of UPMC
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PittsburghUnited StatesUnknown status
Oregon Health and Science University
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PortlandUnited StatesUnknown status
Rhode Island Hospital
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ProvidenceUnited StatesUnknown status
Renown Regional Medical Center
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RenoUnited StatesUnknown status
University of Rochester
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RochesterUnited StatesUnknown status
University of California Davis Comprehensive Cancer Center
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SacramentoUnited StatesUnknown status
Primary Children's Hospital
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Salt Lake CityUnited StatesUnknown status
Children's Hospital of San Antonio
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San AntonioUnited StatesUnknown status
Rady Children's Hospital - San Diego
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San DiegoUnited StatesUnknown status
UCSF Medical Center-Mission Bay
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San FranciscoUnited StatesUnknown status
Memorial Health University Medical Center
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SavannahUnited StatesUnknown status
Maine Children's Cancer Program
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ScarboroughUnited StatesUnknown status
Seattle Children's Hospital
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SeattleUnited StatesUnknown status
Sanford USD Medical Center - Sioux Falls
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Sioux FallsUnited StatesUnknown status
Providence Sacred Heart Medical Center and Children's Hospital
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SpokaneUnited StatesUnknown status
Washington University School of Medicine
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St LouisUnited StatesUnknown status
Mercy Hospital Saint Louis
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St LouisUnited StatesUnknown status
Johns Hopkins All Children's Hospital
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St. PetersburgUnited StatesUnknown status
State University of New York Upstate Medical University
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SyracuseUnited StatesUnknown status
Madigan Army Medical Center
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TacomaUnited StatesUnknown status
Mary Bridge Children's Hospital and Health Center
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TacomaUnited StatesUnknown status
Montefiore Medical Center - Moses Campus
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The BronxUnited StatesUnknown status
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
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ToledoUnited StatesUnknown status
MedStar Georgetown University Hospital
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Washington D.C.United StatesUnknown status
Children's National Medical Center
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Washington D.C.United StatesUnknown status
Saint Mary's Medical Center
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West Palm BeachUnited StatesUnknown status
Alfred I duPont Hospital for Children
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WilmingtonUnited StatesUnknown status
Wake Forest University Health Sciences
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Winston-SalemUnited StatesUnknown status

This page is information, not medical advice. Discuss any trial with your doctor.