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Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

RecruitingPhase 3

A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma

Who can join

Up to age 30 · All sexes

Full eligibility criteria
Inclusion Criteria:

* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* ≤ 30 years at the time of initial diagnosis with high-risk disease
* \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines

  * Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:

    * Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
    * Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
    * Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
    * Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a body surface area (BSA) ≥ 0.25 m\^2
* No prior anti-cancer therapy except as outlined below:

  * Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
  * Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
  * Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex as follows:

  * 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL
  * 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
  * 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
  * 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
  * 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL
  * 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
  * 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
  * ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL

    * The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
  * or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or
  * or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)

    * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\*

  * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* \* Shortening fraction of ≥ 27% by echocardiogram, or

  * Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:

No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure

Exclusion Criteria:

* Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
* Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, food and drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

About the study

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

What is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 478 · Started: Apr 19, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06172296

Locations in the U.S.

AlabamaChildren's Hospital of Alabama, Birmingham
USA Health Strada Patient Care Center, Mobile
ArizonaBanner Children's at Desert, Mesa
Phoenix Childrens Hospital, Phoenix
Banner University Medical Center - Tucson, Tucson
ArkansasArkansas Children's Hospital, Little Rock
CaliforniaKaiser Permanente Downey Medical Center, Downey
City of Hope Comprehensive Cancer Center, Duarte
Loma Linda University Medical Center, Loma Linda
Miller Children's and Women's Hospital Long Beach, Long Beach
Cedars-Sinai Medical Center, Los Angeles
Children's Hospital Los Angeles, Los Angeles
Mattel Children's Hospital UCLA, Los Angeles
Valley Children's Hospital, Madera
Kaiser Permanente-Oakland, Oakland
UCSF Benioff Children's Hospital Oakland, Oakland
Children's Hospital of Orange County, Orange
Lucile Packard Children's Hospital Stanford University, Palo Alto
Sutter Medical Center Sacramento, Sacramento
University of California Davis Comprehensive Cancer Center, Sacramento
Rady Children's Hospital - San Diego, San Diego
UCSF Medical Center-Mission Bay, San Francisco
ColoradoChildren's Hospital Colorado, Aurora
ConnecticutConnecticut Children's Medical Center, Hartford
Yale University, New Haven
DelawareAlfred I duPont Hospital for Children, Wilmington
District of ColumbiaChildren's National Medical Center, Washington D.C.
FloridaBroward Health Medical Center, Fort Lauderdale
Golisano Children's Hospital of Southwest Florida, Fort Myers
UF Health Cancer Institute - Gainesville, Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Nemours Children's Clinic-Jacksonville, Jacksonville
Nicklaus Children's Hospital, Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami
AdventHealth Orlando, Orlando
Arnold Palmer Hospital for Children, Orlando
Nemours Children's Hospital, Orlando
Johns Hopkins All Children's Hospital, St. Petersburg
Saint Mary's Medical Center, West Palm Beach
GeorgiaChildren's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta
Memorial Health University Medical Center, Savannah
HawaiiKapiolani Medical Center for Women and Children, Honolulu
IllinoisLurie Children's Hospital-Chicago, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
University of Illinois, Chicago
Advocate Children's Hospital-Oak Lawn, Oak Lawn
Advocate Children's Hospital-Park Ridge, Park Ridge
OSF Children's Hospital of Illinois, Peoria
Southern Illinois University School of Medicine, Springfield
IndianaRiley Hospital for Children, Indianapolis
IowaBlank Children's Hospital, Des Moines
University of Iowa/Holden Comprehensive Cancer Center, Iowa City
KansasWesley Medical Center, Wichita
KentuckyUniversity of Kentucky/Markey Cancer Center, Lexington
Norton Children's Hospital, Louisville
LouisianaChildren's Hospital New Orleans, New Orleans
MaineEastern Maine Medical Center, Bangor
Maine Children's Cancer Program, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
Sinai Hospital of Baltimore, Baltimore
University of Maryland/Greenebaum Cancer Center, Baltimore
Walter Reed National Military Medical Center, Bethesda
MassachusettsDana-Farber Cancer Institute, Boston
Massachusetts General Hospital Cancer Center, Boston
MichiganC S Mott Children's Hospital, Ann Arbor
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids
Bronson Methodist Hospital, Kalamazoo
Corewell Health Children's, Royal Oak
MinnesotaChildren's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis
University of Minnesota/Masonic Cancer Center, Minneapolis
Mayo Clinic in Rochester, Rochester
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriUniversity of Missouri Children's Hospital, Columbia
Children's Mercy Hospitals and Clinics, Kansas City
Mercy Hospital Saint Louis, St Louis
Washington University School of Medicine, St Louis
NebraskaChildren's Hospital and Medical Center of Omaha, Omaha
University of Nebraska Medical Center, Omaha
NevadaAlliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New JerseyHackensack University Medical Center, Hackensack
Morristown Medical Center, Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick
Saint Peter's University Hospital, New Brunswick
Newark Beth Israel Medical Center, Newark
Saint Joseph's Regional Medical Center, Paterson
New YorkAlbany Medical Center, Albany
Roswell Park Cancer Institute, Buffalo
NYU Langone Hospital - Long Island, Mineola
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York
University of Rochester, Rochester
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
New York Medical College, Valhalla
North CarolinaMission Hospital, Asheville
UNC Lineberger Comprehensive Cancer Center, Chapel Hill
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Novant Health Presbyterian Medical Center, Charlotte
Duke University Medical Center, Durham
East Carolina University, Greenville
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Broadway Medical Center, Fargo
OhioChildren's Hospital Medical Center of Akron, Akron
Cincinnati Children's Hospital Medical Center, Cincinnati
Cleveland Clinic Foundation, Cleveland
Rainbow Babies and Childrens Hospital, Cleveland
Nationwide Children's Hospital, Columbus
Dayton Children's Hospital, Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
Saint Francis Children's Hospital, Tulsa
OregonLegacy Emanuel Children's Hospital, Portland
Oregon Health and Science University, Portland
PennsylvaniaLehigh Valley Hospital-Cedar Crest, Allentown
Geisinger Medical Center, Danville
Children's Hospital of Philadelphia, Philadelphia
Saint Christopher's Hospital for Children, Philadelphia
Children's Hospital of Pittsburgh of UPMC, Pittsburgh
Rhode IslandRhode Island Hospital, Providence
South CarolinaMedical University of South Carolina, Charleston
Prisma Health Richland Hospital, Columbia
BI-LO Charities Children's Cancer Center, Greenville
South DakotaSanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeEast Tennessee Childrens Hospital, Knoxville
Saint Jude Children's Research Hospital, Memphis
The Children's Hospital at TriStar Centennial, Nashville
Vanderbilt University/Ingram Cancer Center, Nashville
TexasDell Children's Medical Center of Central Texas, Austin
Driscoll Children's Hospital, Corpus Christi
Medical City Dallas Hospital, Dallas
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
El Paso Children's Hospital, El Paso
Cook Children's Medical Center, Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston
UT MD Anderson Cancer Center, Houston
Covenant Children's Hospital, Lubbock
UMC Cancer Center / UMC Health System, Lubbock
Children's Hospital of San Antonio, San Antonio
Methodist Children's Hospital of South Texas, San Antonio
University of Texas Health Science Center at San Antonio, San Antonio
UtahPrimary Children's Hospital, Salt Lake City
VermontUniversity of Vermont and State Agricultural College, Burlington
VirginiaUniversity of Virginia Cancer Center, Charlottesville
Naval Medical Center - Portsmouth, Portsmouth
WashingtonSeattle Children's Hospital, Seattle
Providence Sacred Heart Medical Center and Children's Hospital, Spokane
Mary Bridge Children's Hospital and Health Center, Tacoma
West VirginiaEdwards Comprehensive Cancer Center, Huntington
West Virginia University Healthcare, Morgantown
WisconsinUniversity of Wisconsin Carbone Cancer Center - University Hospital, Madison
Marshfield Medical Center-Marshfield, Marshfield
Children's Hospital of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.