Skip to main content

Isotretinoin with or without Dinutuximab, Aldesleukin, and Sargramostim following Stem Cell Transplant in Treating Patients with Neuroblastoma

Trial Status: Closed to Accrual and Intervention

This partially randomized phase III trial studies isotretinoin with dinutuximab, aldesleukin, and sargramostim to see how well it works compared to isotretinoin alone following stem cell transplant in treating patients with neuroblastoma. Drugs used in chemotherapy, such as isotretinoin, 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. Monoclonal antibodies, such as dinutuximab, may block tumor growth in different ways by targeting certain cells. Aldesleukin and sargramostim may stimulate a person's white blood cells to kill cancer cells. It is not yet known if chemotherapy is more effective with or without dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating neuroblastoma.

Inclusion Criteria

  • All patients must be diagnosed with neuroblastoma, and categorized as high risk at the time of diagnosis; exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible
  • All patients must have completed therapy including intensive induction followed by ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor; examples of such therapies include: * Following treatment per A3973 protocol * Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol * Following treatment per CCG3891 * Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02 * Enrollment on or following treatment per ANBL02P1 * Enrollment on or following treatment per ANBL07P1 * Tandem transplant patients are eligible: ** Following treatment on or per ANBL0532 ** Following treatment per POG 9640 ** Following treatment per COG ANBL00P1 ** Following treatment per CHP 594/Dana-Farber Cancer Institute (DFCI) 34-DAT
  • No more than 12 months from the date of starting the first induction chemotherapy after diagnosis to the date of ASCT except for the rare occasions as noted below; for tandem ASCT patients, this will be the date of the FIRST stem cell infusion; exception: for those who are initially diagnosed as non-high risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma, the 12 months restriction should start from the date of induction therapy for high risk neuroblastoma (not from the initial induction therapy for non-high risk disease), to the date of ASCT
  • At pre-ASCT evaluation patients must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone metastases; patients who meet those criteria must also meet the protocol specified criteria for bone marrow response as outlined below: * =< 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy * Patient who have no tumor seen on the prior bone marrow, and then have =< 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible (note that per INRC this would have been defined as “overall” response of progressive disease [PD])
  • Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be performed (tumor imaging studies including computed tomography [CT] or magnetic resonance imaging [MRI], MIBG scan, and vanillylmandelic acid [VMA]/homovanillic acid [HVA]; bone marrow aspirates are required but biopsy may be omitted if negative prior to ASCT); this disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before enrollment * For those with residual disease before radiotherapy, re-evaluation of irradiated residual tumors is preferably performed at the earliest 5 days after completing radiotherapy; patients with residual disease are eligible; biopsy is not required; patients who have biopsy proven residual disease after ASCT will be enrolled on Stratum 07 * Patients must not have progressive disease at the time of study enrollment except for protocol specified bone marrow response and except for elevations of catecholamines as the only sign of disease in a patient who had normal catecholamines at pre-ASCT evaluation
  • Patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than ten (10) calendar days after the date of study enrollment; patients should be enrolled preferably between day 56 and day 85 after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for tandem transplant); patients must be enrolled no later than day 200 after PBSC infusion; enrollment must occur after completion of radiotherapy, and after completion of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained within 3 weeks pre-ASCT up to the time of registration
  • Patients must not have received prior anti-disialoganglioside (GD2) antibody therapy
  • Patients must have a Lansky or Karnofsky performance scale score of >= 50% and patients must have a life expectancy of >= 2 months
  • Total absolute phagocyte count (APC = %neutrophils + %monocytes) X white blood cell (WBC) is at least 1000/uL
  • 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: * No greater than 0.4 mg/dL (1 month to < 6 months) * No greater than 0.5 mg/dL (6 months to < 1 year) * No greater than 0.6 mg/dL (1 to < 2 years) * No greater than 0.8 mg/dL (2 to < 6 years) * No greater than 1.0 mg/dL (6 to < 10 years) * No greater than 1.2 mg/dL (10 to < 13 years) * No greater than 1.4 mg/dL (>= 13 years [female]) * No greater than 1.5 mg/dL (13 to < 16 years [male]) * No greater than 1.7 mg/dL (>= 16 years [male])
  • Total bilirubin =< 1.5 x normal
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x normal
  • Veno-occlusive disease, if present, should be stable or improving
  • Shortening fraction of >= 27% by echocardiogram, or if shortening fraction abnormal, ejection fraction of >= 55% by gated radionuclide study or echocardiogram; note: the echocardiogram or gated radionuclide study must be performed within 4 weeks prior to enrollment
  • Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) > 60% predicted by pulmonary function test; for children who are unable to do pulmonary function tests (PFTs), no evidence of dyspnea at rest and no exercise intolerance should be documented; note: the pulmonary function test must be performed within 4 weeks prior to enrollment
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well-controlled; central nervous system (CNS) toxicity < grade 2
  • Written informed consent in accordance with institutional and Food and Drug Administration (FDA) guidelines must be obtained from parent or legal guardian
  • Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method; female patients who are lactating must agree to stop breast-feeding

Alabama

Birmingham
Children's Hospital of Alabama
Status: CLOSED_TO_ACCRUAL
Contact: Alyssa Terry Reddy
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Alyssa Terry Reddy
Phone: 205-934-0309

Alaska

Anchorage
Providence Alaska Medical Center
Status: COMPLETED
Contact: Judy L. Felgenhauer
Phone: 800-228-6618

Arizona

Phoenix
Phoenix Childrens Hospital
Status: COMPLETED
Contact: Jessica Boklan
Phone: 602-546-0920
Tucson
Banner University Medical Center - Tucson
Status: COMPLETED
Contact: Lisa M. Kopp
Phone: 520-626-9008

Arkansas

Little Rock
Arkansas Children's Hospital
Status: COMPLETED
Contact: David L. Becton
Phone: 501-364-7373
University of Arkansas for Medical Sciences
Status: CLOSED_TO_ACCRUAL
Contact: David L. Becton
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: COMPLETED
Contact: Robert Michael Cooper
Phone: 626-564-3455
Duarte
City of Hope Comprehensive Cancer Center
Status: COMPLETED
Contact: Anna Beata Pawlowska
Phone: 800-826-4673
Loma Linda
Loma Linda University Medical Center
Status: COMPLETED
Contact: Albert Kheradpour
Phone: 909-558-3375
Long Beach
Miller Children's and Women's Hospital Long Beach
Status: COMPLETED
Contact: Theodore Zwerdling
Phone: 562-933-5600
Los Angeles
Children's Hospital Los Angeles
Status: COMPLETED
Contact: Leo Mascarenhas
Phone: 323-361-4110
Madera
Valley Children's Hospital
Status: COMPLETED
Contact: Vonda Lee Crouse
Phone: 866-353-5437
Oakland
Children's Hospital and Research Center at Oakland
Status: COMPLETED
Contact: Carla Barbara Golden
Phone: 510-450-7600
Kaiser Permanente-Oakland
Status: COMPLETED
Contact: Steven K. Bergstrom
Phone: 626-564-3455
Orange
Children's Hospital of Orange County
Status: COMPLETED
Contact: Violet Shen
Phone: 714-997-3000
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: COMPLETED
Contact: Neyssa Maria Marina
Phone: 650-498-7061
Sacramento
Sutter Medical Center Sacramento
Status: CLOSED_TO_ACCRUAL
Contact: Alice Lin-Tsing Yu
Phone: 619-543-2438
University of California Davis Comprehensive Cancer Center
Status: COMPLETED
Contact: Jay Michael S. Balagtas
Phone: 916-734-3089
San Diego
Rady Children's Hospital - San Diego
Status: COMPLETED
Contact: William D. Roberts
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: COMPLETED
Contact: Robert Edward Goldsby
Phone: 877-827-3222
UCSF Medical Center-Parnassus
Status: CLOSED_TO_ACCRUAL
Contact: Robert Edward Goldsby
Phone: 877-827-3222

Colorado

Aurora
Children's Hospital Colorado
Status: COMPLETED
Contact: Brian Scott Greffe
Phone: 720-777-6672
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: COMPLETED
Contact: Jennifer Jocelyn Clark
Phone: 866-775-6246

Connecticut

Hartford
Connecticut Children's Medical Center
Status: COMPLETED
Contact: Michael Scott Isakoff
Phone: 860-545-9981
New Haven
Yale University
Status: COMPLETED
Contact: Nina Singh Kadan-Lottick
Phone: 203-785-5702

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: COMPLETED
Contact: Christopher N. Frantz
Phone: 302-651-5755

District of Columbia

Washington
Children's National Medical Center
Status: COMPLETED
Contact: Jeffrey Stuart Dome
Phone: 202-884-2549
MedStar Georgetown University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Alice Lin-Tsing Yu
Phone: 619-543-2438

Florida

Fort Lauderdale
Broward Health Medical Center
Status: COMPLETED
Contact: Hector M. Rodriguez-Cortes
Phone: 954-355-5346
Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: COMPLETED
Contact: Emad K. Salman
Phone: 239-343-5333
Lee Memorial Health System
Status: CLOSED_TO_ACCRUAL
Contact: Emad K. Salman
Phone: 239-343-5333
Gainesville
University of Florida Health Science Center - Gainesville
Status: COMPLETED
Contact: William Birdsall Slayton
Phone: 352-273-8675
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: COMPLETED
Contact: Iftikhar Hanif
Phone: 954-265-2234
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: COMPLETED
Contact: Scott M. Bradfield
Phone: 904-697-3529
Miami
Miami Cancer Institute
Status: COMPLETED
Contact: Doured Daghistani
Phone: 800-599-2456
Nicklaus Children's Hospital
Status: COMPLETED
Contact: Enrique Alberto Escalon
Phone: 888-624-2778
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: COMPLETED
Contact: Julio Cesar Barredo
Phone: 866-574-5124
Orlando
AdventHealth Orlando
Status: COMPLETED
Contact: Fouad M. Hajjar
Phone: 407-303-5623
Arnold Palmer Hospital for Children
Status: COMPLETED
Contact: Vincent Ferdinando Giusti
Phone: 321-841-7246
Nemours Children's Clinic - Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Phone: 407-650-7150
Nemours Children's Hospital
Status: COMPLETED
Contact: Ramamoorthy Nagasubramanian
Phone: 407-650-7150
UF Cancer Center at Orlando Health
Status: CLOSED_TO_ACCRUAL
Contact: Vincent Ferdinando Giusti
Phone: 321-841-7246
Pensacola
Nemours Children's Clinic - Pensacola
Status: COMPLETED
Contact: Jeffrey H. Schwartz
Phone: 904-697-3529
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: COMPLETED
Contact: Gregory Alan Hale
Phone: 727-767-2423
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: COMPLETED
Contact: Erin Marie Cockrell
Phone: 800-882-4123
West Palm Beach
Saint Mary's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Narayana Gowda

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: COMPLETED
Contact: Glen Lew
Phone: 404-785-1112
Augusta
Augusta University Medical Center
Status: COMPLETED
Contact: Colleen H. McDonough
Phone: 706-721-1663
Savannah
Memorial Health University Medical Center
Status: COMPLETED
Contact: J. Martin Johnston
Phone: 912-350-8568

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: COMPLETED
Contact: Robert W. Wilkinson
Phone: 808-983-6090
Tripler Army Medical Center
Status: COMPLETED
Contact: Jeremy Vaughan Edwards
Phone: 808-433-6336
University of Hawaii Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Robert W. Wilkinson
Phone: 808-983-6090

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: COMPLETED
Contact: Yasmin Castellanes Gosiengfiao
Phone: 773-880-4562
University of Chicago Comprehensive Cancer Center
Status: COMPLETED
Contact: Navin Robert Pinto
Phone: 773-834-7424
University of Illinois
Status: COMPLETED
Contact: Mary Lou Schmidt
Phone: 312-355-3046
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: COMPLETED
Contact: Rebecca Erin McFall
Phone: 847-723-7570
Peoria
Saint Jude Midwest Affiliate
Status: COMPLETED
Contact: Karen Sofia Fernandez
Phone: 309-655-3258
Springfield
Southern Illinois University School of Medicine
Status: COMPLETED
Contact: Gregory P. Brandt
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Robert J. Fallon
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: COMPLETED
Contact: Bassem I. Razzouk
Phone: 317-338-2194

Iowa

Des Moines
Blank Children's Hospital
Status: COMPLETED
Contact: Wendy Leigh Woods-Swafford
Phone: 515-241-6729
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: COMPLETED
Contact: Mariko Sato
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: COMPLETED
Contact: Lars Martin Wagner
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: COMPLETED
Contact: Kenneth G. Lucas
Phone: 866-530-5516

Louisiana

New Orleans
Children's Hospital New Orleans
Status: COMPLETED
Contact: Lolie C. Yu
Phone: 504-894-5377

Maine

Scarborough
Maine Children's Cancer Program
Status: COMPLETED
Contact: Eric C. Larsen
Phone: 207-396-8090

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: COMPLETED
Contact: Allen R. Chen
Phone: 410-955-8804
Sinai Hospital of Baltimore
Status: COMPLETED
Contact: Joseph M. Wiley
Phone: 410-601-6120
University of Maryland / Greenebaum Cancer Center
Status: COMPLETED
Contact: Teresa Anne York
Phone: 800-888-8823
Bethesda
Walter Reed National Military Medical Center
Status: COMPLETED
Contact: Anne Benedicta Warwick
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: COMPLETED
Contact: Carlos Rodriguez-Galindo
Phone: 877-442-3324
Floating Hospital for Children at Tufts Medical Center
Status: COMPLETED
Contact: Michael J. Kelly
Phone: 617-636-5000
Massachusetts General Hospital Cancer Center
Status: COMPLETED
Contact: Howard Jeffrey Weinstein
Phone: 877-726-5130
Springfield
Baystate Medical Center
Status: COMPLETED
Contact: Joanna G. Luty
Phone: 413-794-3565

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: COMPLETED
Contact: Rajen Mody
Phone: 800-865-1125
Detroit
Ascension Saint John Hospital
Status: COMPLETED
Contact: Hadi Sawaf
Phone: 313-343-3166
Wayne State University / Karmanos Cancer Institute
Status: COMPLETED
Contact: Zhihong Joanne Wang
Phone: 313-576-9363
East Lansing
Michigan State University Clinical Center
Status: COMPLETED
Contact: Renuka Gera
Phone: 517-975-9547
Flint
Hurley Medical Center
Status: COMPLETED
Contact: Susumu Inoue
Phone: 888-606-6556
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: COMPLETED
Contact: David Scott Dickens
Phone: 616-267-1925
Kalamazoo
Bronson Methodist Hospital
Status: COMPLETED
Contact: Katharina Elisabeth Elliott
Phone: 800-227-2345

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: COMPLETED
Contact: Michael Kerr Richards
Phone: 612-813-5193
University of Minnesota / Masonic Cancer Center
Status: COMPLETED
Contact: Emily G. Greengard
Phone: 612-624-2620
Rochester
Mayo Clinic in Rochester
Status: COMPLETED
Contact: Carola A. S. Arndt
Phone: 507-538-7623

Mississippi

Jackson
University of Mississippi Medical Center
Status: COMPLETED
Contact: Gail Cranshaw Megason
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: COMPLETED
Contact: Thomas Ward Loew
Phone: 573-882-7440
University of Missouri - Ellis Fischel
Status: WITHDRAWN
Contact: Thomas Ward Loew
Phone: 573-882-7440
Kansas City
Children's Mercy Hospitals and Clinics
Status: COMPLETED
Contact: Maxine Lorraine Hetherington
Phone: 816-234-3265
Saint Louis
Cardinal Glennon Children's Medical Center
Status: COMPLETED
Contact: William Shay Ferguson
Phone: 314-268-4000
Mercy Hospital Saint Louis
Status: COMPLETED
Contact: Bethany Graham Sleckman
Phone: 913-948-5588
Washington University School of Medicine
Status: COMPLETED
Contact: David Brian Wilson
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: COMPLETED
Contact: Minnie Abromowitch
Phone: 402-955-3949
University of Nebraska Medical Center
Status: COMPLETED
Contact: Minnie Abromowitch
Phone: 402-955-3949

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: COMPLETED
Contact: Nik Farahana Nik Abdul Rashid
Phone: 702-384-0013
Nevada Cancer Research Foundation CCOP
Status: CLOSED_TO_ACCRUAL
Contact: Jonathan Bernstein
Phone: 702-384-0013

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: COMPLETED
Contact: Sara Chaffee
Phone: 800-639-6918

New Jersey

Hackensack
Hackensack University Medical Center
Status: COMPLETED
Contact: Burton Eliot Appel
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: COMPLETED
Contact: Steven Lon Halpern
Phone: 973-971-5900
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: COMPLETED
Contact: Richard A. Drachtman
Phone: 732-235-8675
Saint Peter's University Hospital
Status: COMPLETED
Contact: Stanley Calderwood
Phone: 732-745-8600extn6163
Newark
Newark Beth Israel Medical Center
Status: COMPLETED
Contact: Peri Kamalakar
Phone: 973-926-7230
Summit
Overlook Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Steven Lon Halpern
Phone: 973-971-5900

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: COMPLETED
Contact: Koh B. Boayue
Phone: 505-272-6972

New York

Albany
Albany Medical Center
Status: COMPLETED
Contact: Vikramjit Singh Kanwar
Phone: 518-262-3368
Bronx
Montefiore Medical Center - Moses Campus
Status: COMPLETED
Contact: Peter David Cole
Phone: 718-904-2730
Buffalo
Roswell Park Cancer Institute
Status: COMPLETED
Contact: Meghan A. Higman
Phone: 877-275-7724
Mineola
NYU Winthrop Hospital
Status: COMPLETED
Contact: Mark E. Weinblatt
Phone: 866-946-8476
New Hyde Park
The Steven and Alexandra Cohen Children's Medical Center of New York
Status: COMPLETED
Contact: Jonathan D. Fish
Phone: 718-470-3470
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: COMPLETED
Contact: Sharon Leigh Gardner
Phone: 212-263-4434
Mount Sinai Hospital
Status: COMPLETED
Contact: Birte Wistinghausen
Phone: 212-824-7320
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: COMPLETED
Contact: Alice Lee
Phone: 212-305-8615
Rochester
University of Rochester
Status: COMPLETED
Contact: Jeffrey Robert Andolina
Phone: 585-275-5830
Syracuse
State University of New York Upstate Medical University
Status: COMPLETED
Contact: Karol Hicks Kerr
Phone: 315-464-5476
Valhalla
New York Medical College
Status: COMPLETED
Contact: Mehmet Fevzi Ozkaynak
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital
Status: COMPLETED
Contact: Douglas James Scothorn
Phone: 828-213-4150
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: COMPLETED
Contact: Stuart Harrison Gold
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: COMPLETED
Contact: Joel A. Kaplan
Phone: 704-355-2884
Novant Health Presbyterian Medical Center
Status: COMPLETED
Contact: Paulette Charese Bryant
Phone: 704-384-5369
Durham
Duke University Medical Center
Status: COMPLETED
Contact: Susan G. Kreissman
Phone: 888-275-3853
Winston-Salem
Wake Forest University Health Sciences
Status: COMPLETED
Contact: Thomas Williams McLean
Phone: 336-713-6771

North Dakota

Fargo
Sanford Broadway Medical Center
Status: COMPLETED
Contact: Samuel Odame Anim
Phone: 701-234-6161

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: COMPLETED
Contact: Steven J. Kuerbitz
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: COMPLETED
Contact: John Peter Perentesis
Phone: 513-636-2799
Cleveland
Cleveland Clinic Foundation
Status: COMPLETED
Contact: Margaret C. Thompson
Phone: 866-223-8100
Rainbow Babies and Childrens Hospital
Status: COMPLETED
Contact: Yousif (Joe) H. Matloub
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: COMPLETED
Contact: Mark Anthony Ranalli
Phone: 614-722-2708
Dayton
Dayton Children's Hospital
Status: COMPLETED
Contact: Emmett H. Broxson
Phone: 800-228-4055
Toledo
Mercy Children's Hospital
Status: COMPLETED
Contact: Rama Jasty
Phone: 419-251-8210
ProMedica Toledo Hospital / Russell J Ebeid Children's Hospital
Status: COMPLETED
Contact: Jamie L. Dargart
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: COMPLETED
Contact: Rene Yvonne McNall-Knapp
Phone: 405-271-4272

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: COMPLETED
Contact: Janice Faye Olson
Phone: 503-413-2560
Legacy Emanuel Hospital and Health Center
Status: CLOSED_TO_ACCRUAL
Contact: Janice Faye Olson
Phone: 503-413-2560
Oregon Health and Science University
Status: COMPLETED
Contact: Susan Joy Lindemulder
Phone: 503-494-1080

Pennsylvania

Bethlehem
Lehigh Valley Hospital - Muhlenberg
Status: COMPLETED
Contact: Philip M. Monteleone
Phone: 484-884-2201
Danville
Geisinger Medical Center
Status: COMPLETED
Contact: Jagadeesh Ramdas
Phone: 570-271-5251
Hershey
Penn State Children's Hospital
Status: COMPLETED
Contact: Lisa MacNabb McGregor
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: COMPLETED
Contact: John M. Maris
Phone: 215-590-2810
Saint Christopher's Hospital for Children
Status: COMPLETED
Contact: Akash Nahar
Phone: 215-427-8991
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: COMPLETED
Contact: Jean M. Tersak
Phone: 412-692-5573

Puerto Rico

San Juan
San Jorge Children's Hospital
Status: COMPLETED
Contact: Luis A. Clavell
Phone: 787-765-2363

Rhode Island

Providence
Rhode Island Hospital
Status: COMPLETED
Contact: Jennifer J. Greene Welch
Phone: 401-444-1488

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED
Contact: Jacqueline M. Kraveka
Phone: 843-792-9321
Columbia
Prisma Health Richland Hospital
Status: COMPLETED
Contact: Ronnie W. Neuberg
Phone: 803-434-3680
Greenville
BI-LO Charities Children's Cancer Center
Status: COMPLETED
Contact: Nichole Leigh Bryant
Phone: 864-241-6251
Greenville Cancer Treatment Center
Status: CLOSED_TO_ACCRUAL
Contact: Cary E. Stroud
Phone: 864-241-6251

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: COMPLETED
Contact: Kayelyn Jean Wagner
Phone: 605-328-1367

Tennessee

Chattanooga
T C Thompson Children's Hospital
Status: COMPLETED
Contact: Manoo G. Bhakta
Phone: 423-778-7289
Knoxville
East Tennessee Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ray C. Pais
Phone: 865-541-8266
Memphis
Saint Jude Children's Research Hospital
Status: COMPLETED
Contact: Wayne Lee Furman
Phone: 866-278-5833
Nashville
Vanderbilt University / Ingram Cancer Center
Status: COMPLETED
Contact: Howard Mark Katzenstein
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: COMPLETED
Contact: Sharon Kay Lockhart
Phone: 512-324-8022
Corpus Christi
Driscoll Children's Hospital
Status: COMPLETED
Contact: M. Cris Johnson
Phone: 361-694-5311
Dallas
Medical City Dallas Hospital
Status: COMPLETED
Contact: Stanton Carl Goldman
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: COMPLETED
Contact: Tanya Carens Watt
Phone: 214-648-7097
Fort Worth
Cook Children's Medical Center
Status: COMPLETED
Contact: Mary Meaghan Petty Granger
Phone: 682-885-2103
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: COMPLETED
Contact: Karen Ruth Rabin
Phone: 713-798-1354
San Antonio
Methodist Children's Hospital of South Texas
Status: COMPLETED
Contact: Jaime Estrada
Phone: 210-575-7000
University of Texas Health Science Center at San Antonio
Status: COMPLETED
Contact: Anne-Marie R. Langevin
Phone: 210-450-3800

Utah

Salt Lake City
Primary Children's Hospital
Status: COMPLETED
Contact: Phillip Evan Barnette
Phone: 801-585-5270

Vermont

Burlington
University of Vermont and State Agricultural College
Status: COMPLETED
Contact: Alan Charles Homans
Phone: 802-656-4101

Virginia

Charlottesville
University of Virginia Cancer Center
Status: COMPLETED
Contact: Kimberly Panter Dunsmore
Phone: 434-243-6143
Falls Church
Inova Fairfax Hospital
Status: COMPLETED
Contact: Marshall A. Schorin
Phone: 703-208-6650
Norfolk
Children's Hospital of The King's Daughters
Status: COMPLETED
Contact: Eric Jeffrey Lowe
Phone: 757-668-7243
Portsmouth
Naval Medical Center - Portsmouth
Status: COMPLETED
Contact: Bethany Michelle Mikles
Phone: 757-953-5939
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: COMPLETED
Contact: Gita Vasers Massey
Phone: 804-628-1939
Roanoke
Carilion Children's
Status: COMPLETED
Contact: Mandy M Atkinson
Phone: 540-981-7376

Washington

Seattle
Seattle Children's Hospital
Status: COMPLETED
Contact: Douglas S. Hawkins
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: COMPLETED
Contact: Judy L. Felgenhauer
Phone: 800-228-6618

West Virginia

Morgantown
West Virginia University Healthcare
Status: CLOSED_TO_ACCRUAL
Contact: Alice Lin-Tsing Yu
Phone: 619-543-2438

Wisconsin

Green Bay
Saint Vincent Hospital Cancer Center Green Bay
Status: COMPLETED
Contact: John Robert Hill
Phone: 920-433-8889
Madison
University of Wisconsin Hospital and Clinics
Status: COMPLETED
Contact: Kenneth Brian De Santes
Phone: 608-262-5223
Marshfield
Marshfield Medical Center-Marshfield
Status: COMPLETED
Contact: Michael John McManus
Phone: 715-389-4457
Milwaukee
Children's Hospital of Wisconsin
Status: COMPLETED
Contact: Michael Edward Kelly
Phone: 414-805-4380

Alberta

Calgary
Alberta Children's Hospital
Status: COMPLETED
Contact: Douglas R. Strother
Phone: 403-220-6898
Edmonton
University of Alberta Hospital
Status: COMPLETED
Contact: Sunil Jayantilal Sunderlal Desai
Phone: 780-407-6615

British Columbia

Vancouver
British Columbia Children's Hospital
Status: COMPLETED
Contact: Caron Strahlendorf
Phone: 604-875-2345extn6477

Manitoba

Winnipeg
CancerCare Manitoba
Status: COMPLETED
Contact: Rochelle Avis Yanofsky
Phone: 866-561-1026

Newfoundland and Labrador

Saint John's
Janeway Child Health Centre
Status: COMPLETED
Contact: Lisa Anne Goodyear
Phone: 866-722-1126

Nova Scotia

Halifax
IWK Health Centre
Status: COMPLETED
Contact: Conrad Vincent Fernandez
Phone: 902-470-8394

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: COMPLETED
Contact: Carol A. Portwine
Phone: 905-521-2100extn74595
London
Children's Hospital
Status: COMPLETED
Contact: Shayna M. Zelcer
Phone: 519-685-8306
Ottawa
Children's Hospital of Eastern Ontario
Status: COMPLETED
Contact: Jacqueline Mary Lewis Halton
Phone: 613-738-3931
Toronto
Hospital for Sick Children
Status: COMPLETED
Contact: Sarah Weeks Alexander
Phone: 416-813-7654extn2027

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: COMPLETED
Contact: Yvan Samson
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: COMPLETED
Contact: Sharon Barbara Abish
Phone: 514-412-4445
Quebec
Centre Hospitalier Universitaire de Quebec
Status: COMPLETED
Contact: Bruno Michon
Phone: 418-525-4444

Australia

Herston
Royal Brisbane and Women's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923
Royal Children's Hospital-Brisbane
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923
Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: COMPLETED
Contact: Geoffrey Brian McCowage
Phone: 61-2-9845 1400
North Adelaide
Women's and Children's Hospital-Adelaide
Status: COMPLETED
Contact: Maria Louise Kirby
Phone: (08) 8161 7327
Parkville
Royal Children's Hospital
Status: COMPLETED
Contact: Francoise Marie Mechinaud
Perth
Princess Margaret Hospital for Children
Status: COMPLETED
Contact: Catherine Helen Cole
Phone: (08) 9340 8222
Randwick
Sydney Children's Hospital
Status: COMPLETED
Contact: Geoffrey Brian McCowage
Phone: 61-2-9845 1400
South Brisbane
Queensland Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Helen Irving
Westmead
The Children's Hospital at Westmead
Status: COMPLETED
Contact: Geoffrey Brian McCowage
Phone: 61-2-9845 1400

New Zealand

Christchurch
Christchurch Hospital
Status: COMPLETED
Contact: Siobhan Frances Cross
Phone: +03 364 0640
Grafton
Starship Children's Hospital
Status: COMPLETED
Contact: Lochie Rodrick Teague
Phone: +0800 728 436

PRIMARY OBJECTIVES:

I. Determine if monoclonal antibody Ch14.18 (dinutuximab) + cytokines + isotretinoin (13-cis-retinoic acid, or RA) improves event free survival after myeloablative therapy and stem cell rescue as compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-autologous stem cell transplant (ASCT) response of complete response (CR), very good partial response (VGPR), or partial response (PR).

SECONDARY OBJECTIVES:

I. Determine if monoclonal antibody Ch14.18 + cytokines + isotretinoin (13-cis-retinoic acid, or RA) improves overall survival after myeloablative therapy and stem cell rescue as compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-ASCT response of CR, VGPR, or PR.

II. Determine if immunotherapy + RA improves event free survival and overall survival as compared to RA alone, in the subgroup of high risk International Neuroblastoma Staging System (INSS) stage 4 neuroblastoma patients who have achieved a pre-ASCT response of CR, VGPR, or PR.

III. Determine the toxicities of the combination of monoclonal antibody Ch14.18 with cytokines.

IV. To compare the outcome data of the patients with persistent disease documented by biopsy (Stratum 07) to the historical data for the analogous patients from Children's Cancer Group (CCG)-3981.

V. To further describe and refine the event free survival (EFS) and overall survival (OS) estimates and baseline characteristics for subjects receiving Ch14.18 + cytokines + RA, following cessation of the randomized portion of the study.

VI. To further describe the safety and toxicity of Ch14.18 + cytokines + RA under the new administration guidelines implemented following cessation of the randomized portion of the study with focus on: a) number of courses delivered per subject; b) number of dose reductions or stoppage (ch14.18 and/or interleukin [IL]-2); and c) number of toxic deaths.

TERTIARY OBJECTIVES:

I. In the subgroup of neuroblastoma patients who have achieved a pre-ASCT response of CR, VGPR, or PR, determine if there is a difference between the two randomized regimens in reducing the minimal residual disease (MRD) burden as detected by the following parameters: meta-iodobenylguanidine (MIBG) scan, immunocytology (IC) of blood and bone marrow samples, reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase, phosphoglycolate phosphatase (PGP) 9.5, and melanoma antigen family A, 1 (MAGE-1) in blood and bone marrow.

II. Determine if change from baseline of MRD is associated with event free and overall survival.

III. Determine whether tumor biology at diagnosis correlates with event-free and overall survival, for either of the randomized regimens.

IV. To explore the relationship between antibody-dependent cellular cytoxicity (ADCC) and EFS.

V. To determine a descriptive profile of human anti-chimeric antibody (HACA) during immunotherapy.

VI. To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels and/or genetic variations correlate with EFS or systemic toxicity.

VII. To determine the potential effect of ch14.18 on cardiac repolarization and to evaluate ch14.18 plasma levels.

VIII. To determine if the presence of naturally occurring anti-glycan antibodies correlates with allergic reactions and blood levels of ch14.18.

IX. To determine if the genotype of Fc receptor (FcR) and killer cell immunoglobulin-like receptor (Kir)/Kir-ligand correlate with EFS.

X. To determine if natural killer cell p30-related protein (NKp30) isoform expression and single nucleotide polymorphism (SNP), and circulating ligand B7-H6 are prognostic of EFS or OS.

OUTLINE: Patients stratified with biopsy-confirmed post-ASCT persistent disease who are also enrolled on Children's Oncology Group (COG)-A3973 or COG-ANBL0532 are assigned to treatment Arm II. Patients in the first set of strata are randomized to 1 of 2 treatment arms.

ARM I: Beginning on day 56-85 post-ASCT, patients receive isotretinoin orally (PO) twice daily (BID) for 14 days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy. (closed to accrual as of 4/16/2009)

ARM II: Beginning on day 56-85 post-ASCT, patients receive immunotherapy comprising sargramostim (GM-CSF) subcutaneously (SC) or intravenously (IV) over 2 hours on days 0-13 during courses 1, 3, and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5. Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy.

After completion of study treatment, patients are followed up periodically for 10 years.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Alice Lin-Tsing Yu

  • Primary ID ANBL0032
  • Secondary IDs NCI-2009-01064, s14-01661, COG-ANBL0032, PANBL0032_A33PAMDREVW01, CDR0000069018
  • Clinicaltrials.gov ID NCT00026312