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

Registration Number: NCT06172296

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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 GD...

Detailed Description: PRIMARY OBJECTIVE:

I. To determine if the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma assigned to early chemoimmunotherapy during Induction differs from that of patients who are not assigned to treatment that includes early chemoimmunotherapy.

SECONDARY OBJECTIVES:
...

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 478

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 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 derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the CDC or
- a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (SOC treatment)	Topotecan	See detailed description
Arm A (SOC treatment)	Tumor Resection	See detailed description
Arm B (Dinutuximab in induction)	Tumor Resection	See detailed description
Arm B (Dinutuximab in induction)	Leukapheresis	See detailed description
Arm A (SOC treatment)	Biospecimen Collection	See detailed description
Arm A (SOC treatment)	Bone Marrow Aspiration	See detailed description
Arm A (SOC treatment)	Bone Marrow Biopsy	See detailed description
Arm A (SOC treatment)	Cisplatin	See detailed description
Arm A (SOC treatment)	Computed Tomography	See detailed description
Arm B (Dinutuximab in induction)	Magnetic Resonance Imaging	See detailed description
Arm A (SOC treatment)	FDG-Positron Emission Tomography and Computed Tomography Scan	See detailed description
Arm A (SOC treatment)	Hematopoietic Cell Transplantation	See detailed description
Arm A (SOC treatment)	Leukapheresis	See detailed description
Arm A (SOC treatment)	Magnetic Resonance Imaging	See detailed description
Arm A (SOC treatment)	Radiation Therapy	See detailed description
Arm A (SOC treatment)	Radionuclide Imaging	See detailed description
Arm A (SOC treatment)	Survey Administration	See detailed description
Arm B (Dinutuximab in induction)	Biospecimen Collection	See detailed description
Arm B (Dinutuximab in induction)	Bone Marrow Aspiration	See detailed description
Arm B (Dinutuximab in induction)	Bone Marrow Biopsy	See detailed description
Arm B (Dinutuximab in induction)	Computed Tomography	See detailed description
Arm B (Dinutuximab in induction)	Etoposide	See detailed description
Arm B (Dinutuximab in induction)	FDG-Positron Emission Tomography and Computed Tomography Scan	See detailed description
Arm B (Dinutuximab in induction)	Hematopoietic Cell Transplantation	See detailed description
Arm B (Dinutuximab in induction)	Irinotecan	See detailed description
Arm B (Dinutuximab in induction)	Radiation Therapy	See detailed description
Arm B (Dinutuximab in induction)	Radionuclide Imaging	See detailed description
Arm B (Dinutuximab in induction)	Survey Administration	See detailed description
Arm A (SOC treatment)	Doxorubicin	See detailed description
Arm A (SOC treatment)	Dinutuximab	See detailed description
Arm A (SOC treatment)	Carboplatin	See detailed description
Arm A (SOC treatment)	Cyclophosphamide	See detailed description
Arm A (SOC treatment)	Etoposide	See detailed description
Arm A (SOC treatment)	Irinotecan	See detailed description
Arm A (SOC treatment)	Isotretinoin	See detailed description
Arm A (SOC treatment)	Melphalan	See detailed description
Arm A (SOC treatment)	Temozolomide	See detailed description
Arm A (SOC treatment)	Thiotepa	See detailed description
Arm A (SOC treatment)	Vincristine	See detailed description
Arm B (Dinutuximab in induction)	Cisplatin	See detailed description
Arm B (Dinutuximab in induction)	Carboplatin	See detailed description
Arm B (Dinutuximab in induction)	Dinutuximab	See detailed description
Arm B (Dinutuximab in induction)	Cyclophosphamide	See detailed description
Arm B (Dinutuximab in induction)	Melphalan	See detailed description
Arm B (Dinutuximab in induction)	Doxorubicin	See detailed description
Arm B (Dinutuximab in induction)	Isotretinoin	See detailed description
Arm B (Dinutuximab in induction)	Thiotepa	See detailed description
Arm B (Dinutuximab in induction)	Temozolomide	See detailed description
Arm B (Dinutuximab in induction)	Topotecan	See detailed description
Arm B (Dinutuximab in induction)	Vincristine	See detailed description

Primary Outcome Measures

Name	Time	Method
Event free survival (EFS)	Up to 3 years	EFS time is calculated from time of randomization to Arms A or B to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 2 years	The proportion of patients with at least one grade 3 or higher non-hematologic toxicity or grade 4 or higher hematologic toxicity during protocol therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, will be reported.
GD2 expression	Up to 12 months	Dinutuximab binding to pre-therapy patient tumor samples will be measured and categorized as high or low.
End of Induction (EOI) response rate	From randomization to end of extended Induction, up to 12 months	The response rate will be calculated among all evaluable patients at end of Induction. Responders are defined as patients who achieve a \>= partial response (PR) per the revised 2017 International Neuroblastoma Response Criteria (INRC)
Overall survival (OS)	Up to 3 years	OS time is calculated from time of randomization to Arms A or B until death, or until last contact if patient is alive.

Trial Locations

Locations (118): Blank Children's Hospital
🇺🇸
Des Moines, Iowa, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Children's Hospital of Alabama
🇺🇸
Birmingham, Alabama, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸
Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Valley Children's Hospital
🇺🇸
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸
Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Golisano Children's Hospital of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville
🇺🇸
Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸
Jacksonville, Florida, United States
Nicklaus Children's Hospital
🇺🇸
Miami, Florida, United States
Arnold Palmer Hospital for Children
🇺🇸
Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸
Orlando, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
🇺🇸
Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸
Oak Lawn, Illinois, United States
Advocate Children's Hospital-Park Ridge
🇺🇸
Park Ridge, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸
Springfield, Illinois, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
University of Iowa/Holden Comprehensive Cancer Center
🇺🇸
Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
🇺🇸
Lexington, Kentucky, United States
Eastern Maine Medical Center
🇺🇸
Bangor, Maine, United States
Maine Children's Cancer Program
🇺🇸
Scarborough, Maine, United States
Sinai Hospital of Baltimore
🇺🇸
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Children's Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
🇺🇸
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Corewell Health Children's
🇺🇸
Royal Oak, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸
Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
🇺🇸
Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha
🇺🇸
Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸
Lebanon, New Hampshire, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸
Paterson, New Jersey, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸
Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
NYU Langone Hospital - Long Island
🇺🇸
Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
🇺🇸
New York, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸
Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Dayton Children's Hospital
🇺🇸
Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
🇺🇸
Toledo, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States
Prisma Health Richland Hospital
🇺🇸
Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center
🇺🇸
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
🇺🇸
Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸
Dallas, Texas, United States
El Paso Children's Hospital
🇺🇸
El Paso, Texas, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Covenant Children's Hospital
🇺🇸
Lubbock, Texas, United States
UMC Cancer Center / UMC Health System
🇺🇸
Lubbock, Texas, United States
Children's Hospital of San Antonio
🇺🇸
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸
Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸
Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸
Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Perth Children's Hospital
🇦🇺
Perth, Western Australia, Australia
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
IWK Health Centre
🇨🇦
Halifax, Nova Scotia, Canada
Children's Hospital
🇨🇦
London, Ontario, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
🇨🇦
Sherbrooke, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
🇨🇦
Quebec, Canada
Starship Children's Hospital
🇳🇿
Grafton, Auckland, New Zealand

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

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts