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Promising new drug combo gives hope for kids with relapsed neuroblastoma

NCT ID NCT03794349

Disease control Sponsor: Children's Oncology Group Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests whether adding eflornithine (DFMO) to a standard chemotherapy and immunotherapy regimen can improve outcomes for children with neuroblastoma that has returned or is not responding to treatment. About 94 children will be randomly assigned to receive the standard treatment with or without DFMO. The goal is to see if the combination shrinks tumors or slows disease progression.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

94 people

The number who actually took part.

Started

Jul 2019

Expected to finish

Mar 2029

An estimate. End dates often move.

Lead sponsor

A research network

The lead sponsor is a research network or cooperative group.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

1 year and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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. Exclusion Criteria: * 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 with only elevated catecholamines (i.e. \> 2 x ULN) are NOT 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 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 \>= grade 2 diarrhea. * 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. * 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.

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Conditions

The condition(s) this trial relates to.

neuroblastoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

High-risk neuroblastoma Recurrent neuroblastoma Refractory neuroblastoma

Contacts and locations

Locations

Albany Medical Center

Albany, New York, 12208, United States
Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States
Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States
Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States
Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States
BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States
Blank Children's Hospital

Des Moines, Iowa, 50309, United States
Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States
C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, G1V 4G2, Canada
CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada
Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States
Cedars Sinai Medical Center

Los Angeles, California, 90048, United States
Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada
Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States
Children's Hospital

London, Ontario, N6A 5W9, Canada
Children's Hospital Colorado

Aurora, Colorado, 80045, United States
Children's Hospital Los Angeles

Los Angeles, California, 90027, United States
Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States
Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States
Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States
Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States
Children's Hospital of Michigan

Detroit, Michigan, 48201, United States
Children's Hospital of Orange County

Orange, California, 92868, United States
Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States
Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States
Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States
Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States
Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States
Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States
Christchurch Hospital

Christchurch, 8011, New Zealand
Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States
Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States
Cook Children's Medical Center

Fort Worth, Texas, 76104, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Dayton Children's Hospital

Dayton, Ohio, 45404, United States
Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States
Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States
Eastern Maine Medical Center

Bangor, Maine, 04401, United States
Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States
HIMA San Pablo Oncologic Hospital

Caguas, 00726, Puerto Rico
Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States
Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada
IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada
Janeway Child Health Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada
John Hunter Children's Hospital

Hunter Regional Mail Centre, New South Wales, 2310, Australia
Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States
Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States
Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States
Kaiser Permanente-Oakland

Oakland, California, 94611, United States
Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States
Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada
Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103, United States
Loyola University Medical Center

Maywood, Illinois, 60153, United States
Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States
Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States
Madigan Army Medical Center

Tacoma, Washington, 98431, United States
Maine Children's Cancer Program

Scarborough, Maine, 04074, United States
Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States
McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada
MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States
Medical City Dallas Hospital

Dallas, Texas, 75230, United States
Memorial Health University Medical Center

Savannah, Georgia, 31404, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States
Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States
Michigan State University

East Lansing, Michigan, 48823, United States
Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States
Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States
Morristown Medical Center

Morristown, New Jersey, 07960, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States
NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States
Nationwide Children's Hospital

Columbus, Ohio, 43205, United States
Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States
Nemours Children's Hospital

Orlando, Florida, 32827, United States
Nicklaus Children's Hospital

Miami, Florida, 33155, United States
Norton Children's Hospital

Louisville, Kentucky, 40202, United States
Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States
Oregon Health and Science University

Portland, Oregon, 97239, United States
Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States
Perth Children's Hospital

Perth, Western Australia, 6009, Australia
Primary Children's Hospital

Salt Lake City, Utah, 84113, United States
Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, 43606, United States
Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States
Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia
Rady Children's Hospital - San Diego

San Diego, California, 92123, United States
Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States
Renown Regional Medical Center

Reno, Nevada, 89502, United States
Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Riley Hospital for Children

Indianapolis, Indiana, 46202, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Royal Children's Hospital

Parkville, Victoria, 3052, Australia
Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States
Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States
Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States
Saint Mary's Medical Center

West Palm Beach, Florida, 33407, United States
Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States
Seattle Children's Hospital

Seattle, Washington, 98105, United States
Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States
Starship Children's Hospital

Grafton, Auckland, 1145, New Zealand
State University of New York Upstate Medical University

Syracuse, New York, 13210, United States
Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States
Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States
Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia
The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States
The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia
The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada
The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States
UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States
UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States
University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States
University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States
University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States
University of Illinois

Chicago, Illinois, 60612, United States
University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States
University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States
University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States
University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of Rochester

Rochester, New York, 14642, United States
University of Vermont and State Agricultural College

Burlington, Vermont, 05405, United States
University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
Valley Children's Hospital

Madera, California, 93636, United States
Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States
Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States
West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States
Women's and Children's Hospital-Adelaide

North Adelaide, South Australia, 5006, Australia
Yale University

New Haven, Connecticut, 06520, United States

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