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Irinotecan Hydrochloride, Temozolomide, and Dinutuximab with or without Eflornithine in Treating Patients with Relapsed or Refractory Neuroblastoma

Trial Status: Temporarily Closed to Accrual

This phase II trial studies how well irinotecan hydrochloride (irinotecan), temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back or that isn't responding to treatment. 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.

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. Patients must have ONE of the following: * First episode of recurrent disease following completion of aggressive multi-drug frontline therapy. * First episode of progressive 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 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 platelet count criteria are met. 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.

Alabama

Birmingham
Children's Hospital of Alabama
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 205-638-9285

Arkansas

Little Rock
Arkansas Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 626-564-3455
Los Angeles
Cedars Sinai Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 310-423-8965
Children's Hospital Los Angeles
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 323-361-4110
Oakland
Kaiser Permanente-Oakland
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org
Orange
Children's Hospital of Orange County
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 714-997-3000
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-694-0012
Sacramento
University of California Davis Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 916-734-3089
San Diego
Rady Children's Hospital - San Diego
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-827-3222

Colorado

Aurora
Children's Hospital Colorado
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 303-764-5056
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 303-839-6000

Connecticut

Hartford
Connecticut Children's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 860-545-9981
New Haven
Yale University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 203-785-5702

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 202-444-2223

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 239-343-5333
Gainesville
University of Florida Health Science Center - Gainesville
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 352-273-8010
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 954-265-1847
Email: OHR@mhs.net
Miami
Nicklaus Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-624-2778
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
Arnold Palmer Hospital for Children
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 321-843-2584
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 727-767-4784
West Palm Beach
Saint Mary's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 561-881-2815

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 404-785-2025
Savannah
Memorial Health University Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 912-350-7887

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 808-983-6090

Idaho

Boise
Saint Luke's Mountain States Tumor Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 208-381-2774

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 312-355-3046
Peoria
Saint Jude Midwest Affiliate
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-226-4343

Indiana

Indianapolis
Riley Hospital for Children
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 317-338-2194

Iowa

Des Moines
Blank Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 515-241-8912
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 502-629-5500

Louisiana

New Orleans
Children's Hospital New Orleans
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Ochsner Medical Center Jefferson
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 504-703-8712

Maine

Bangor
Eastern Maine Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 207-973-4274

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 410-955-8804
Sinai Hospital of Baltimore
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 410-601-6120

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 877-442-3324

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-865-1125
East Lansing
Michigan State University Clinical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 517-975-9547

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 612-624-2620

Mississippi

Jackson
University of Mississippi Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Kansas City
Children's Mercy Hospitals and Clinics
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu
Saint Louis
Mercy Hospital Saint Louis
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 314-251-7066
Washington University School of Medicine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 402-955-3949
University of Nebraska Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 402-559-6941

New Jersey

Morristown
Morristown Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 973-971-5900

New York

Albany
Albany Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 518-262-5513
Bronx
Montefiore Medical Center - Moses Campus
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 718-379-6866
Buffalo
Roswell Park Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-767-9355
New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 212-305-6361
Rochester
University of Rochester
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 585-275-5830
Syracuse
State University of New York Upstate Medical University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 315-464-5476

North Carolina

Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-804-9376
Durham
Duke University Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-275-3853
Winston-Salem
Wake Forest University Health Sciences
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 513-636-2799
Cleveland
Cleveland Clinic Foundation
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-223-8100
Rainbow Babies and Childrens Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 614-072-2657
Dayton
Dayton Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-228-4055
Toledo
ProMedica Toledo Hospital / Russell J Ebeid Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 405-271-8777

Oregon

Portland
Oregon Health and Science University
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 503-494-1080

Pennsylvania

Allentown
Lehigh Valley Hospital-Cedar Crest
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 734-712-3671
Hershey
Penn State Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 267-425-5544
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 412-692-8570

Rhode Island

Providence
Rhode Island Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 401-444-1488

South Carolina

Columbia
Prisma Health Richland Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 803-434-3533

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 605-312-3320

Tennessee

Knoxville
East Tennessee Childrens Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
Saint Jude Children's Research Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-226-4343
Nashville
The Children's Hospital at TriStar Centennial
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 615-342-1919
Vanderbilt University / Ingram Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 512-628-1902
Corpus Christi
Driscoll Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 361-694-5311
Dallas
Medical City Dallas Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 214-648-7097
Fort Worth
Cook Children's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 682-885-2103
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 713-798-1354
San Antonio
Children's Hospital of San Antonio
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
University of Texas Health Science Center at San Antonio
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 210-450-3800

Utah

Salt Lake City
Primary Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 801-585-5270

Vermont

Burlington
University of Vermont and State Agricultural College
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 802-656-8990
Email: rpo@uvm.edu

Virginia

Norfolk
Children's Hospital of The King's Daughters
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 757-668-7243

Washington

Seattle
Seattle Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-228-6618

West Virginia

Morgantown
West Virginia University Healthcare
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 304-293-7374

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 800-622-8922
Milwaukee
Children's Hospital of Wisconsin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 414-955-4727

Manitoba

Winnipeg
CancerCare Manitoba
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 866-561-1026

Nova Scotia

Halifax
IWK Health Centre
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 902-470-6767

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 514-412-4445

Australia

Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (02) 4985 5180
North Adelaide
Women's and Children's Hospital-Adelaide
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (08) 8161 7327
Randwick
Sydney Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: (02) 9382-1721
South Brisbane
Queensland Children's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 61 7 3068 1111
Westmead
The Children's Hospital at Westmead
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 61-2-9845 1400

New Zealand

Christchurch
Christchurch Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 03 364 0640

PRIMARY OBJECTIVES:

I. To determine whether administration of eflornithine (DFMO) in combination with dinutuximab, irinotecan hydrochloride (irinotecan) and temozolomide results in an improved response rate compared to dinutuximab, irinotecan and temozolomide in patients with relapsed or refractory neuroblastoma and therefore is a therapeutic regimen worthy of further testing in patients with newly-diagnosed high-risk neuroblastoma.

SECONDARY OBJECTIVES:

I. To compare progression-free survival and overall survival between patients receiving dinutuximab, irinotecan and temozolomide with and without the addition of DFMO.

II. To define the toxicity profile of DFMO administered with dinutuximab, irinotecan and temozolomide.

EXPLORATORY OBJECTIVES:

I. To characterize the immune and cytokine profiles of patients treated with DFMO/chemotherapy/dinutuximab combination and correlate with response to therapy.

II. To evaluate GD2 levels in tumor cells from patient bone marrow samples and correlate with response to therapy.

III. To explore whether the addition of DFMO to the dinutuximab and chemotherapy backbone affects pain as determined by patient report and opiate usage.

OUTLINE: Patients are randomized to 1 of 2 regimens.

REGIMEN A: Patients receive temozolomide orally (PO), via nasogastric (NG), or gastric (G) tube on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) or IV over 2 hours on days 6-12 of a 21-day cycle. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

REGIMEN B: Patients receive eflornithine PO, via NG, or G tube on days -6 to 21 of cycle 1 and days 1-21 of subsequent cycles, temozolomide PO, via NG, or G tube on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC or IV over 2 hours on days 6-12. Treatment lasts 28 days for cycle 1 and then every 21 days for subsequent cycles up to 17 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and periodically for 5 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Margaret Ellen Macy

  • Primary ID ANBL1821
  • Secondary IDs NCI-2018-03377
  • Clinicaltrials.gov ID NCT03794349