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

Status: Recruiting
Location: See all (170) locations...
Intervention Type: Procedure, Drug, Other, Biological, Radiation
Study Type: Interventional
Study Phase: Phase 3
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 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.

Eligibility
Participation Requirements
Sex: All
Maximum Age: 30
Healthy Volunteers: f
View:

• 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

⁃ ≥ 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

Locations
United States
Alabama
Children's Hospital of Alabama
RECRUITING
Birmingham
USA Health Strada Patient Care Center
RECRUITING
Mobile
Arkansas
Arkansas Children's Hospital
RECRUITING
Little Rock
Arizona
Banner Children's at Desert
RECRUITING
Mesa
Phoenix Childrens Hospital
RECRUITING
Phoenix
Banner University Medical Center - Tucson
RECRUITING
Tucson
California
Kaiser Permanente Downey Medical Center
RECRUITING
Downey
City of Hope Comprehensive Cancer Center
RECRUITING
Duarte
Loma Linda University Medical Center
RECRUITING
Loma Linda
Miller Children's and Women's Hospital Long Beach
RECRUITING
Long Beach
Cedars Sinai Medical Center
RECRUITING
Los Angeles
Children's Hospital Los Angeles
RECRUITING
Los Angeles
Mattel Children's Hospital UCLA
RECRUITING
Los Angeles
Valley Children's Hospital
RECRUITING
Madera
Kaiser Permanente-Oakland
RECRUITING
Oakland
UCSF Benioff Children's Hospital Oakland
RECRUITING
Oakland
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
RECRUITING
Palo Alto
Sutter Medical Center Sacramento
RECRUITING
Sacramento
University of California Davis Comprehensive Cancer Center
RECRUITING
Sacramento
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Connecticut
Connecticut Children's Medical Center
RECRUITING
Hartford
Yale University
RECRUITING
New Haven
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington D.c.
Delaware
Alfred I duPont Hospital for Children
RECRUITING
Wilmington
Florida
Broward Health Medical Center
RECRUITING
Fort Lauderdale
Golisano Children's Hospital of Southwest Florida
RECRUITING
Fort Myers
University of Florida Health Science Center - Gainesville
RECRUITING
Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
RECRUITING
Hollywood
Nemours Children's Clinic-Jacksonville
RECRUITING
Jacksonville
Nicklaus Children's Hospital
RECRUITING
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
AdventHealth Orlando
RECRUITING
Orlando
Arnold Palmer Hospital for Children
RECRUITING
Orlando
Nemours Children's Hospital
RECRUITING
Orlando
Johns Hopkins All Children's Hospital
RECRUITING
St. Petersburg
Saint Mary's Medical Center
RECRUITING
West Palm Beach
Georgia
Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITING
Atlanta
Hawaii
Kapiolani Medical Center for Women and Children
RECRUITING
Honolulu
Iowa
Blank Children's Hospital
RECRUITING
Des Moines
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Illinois
Lurie Children's Hospital-Chicago
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Advocate Children's Hospital-Oak Lawn
RECRUITING
Oak Lawn
Advocate Children's Hospital-Park Ridge
RECRUITING
Park Ridge
Saint Jude Midwest Affiliate
RECRUITING
Peoria
Southern Illinois University School of Medicine
RECRUITING
Springfield
Indiana
Riley Hospital for Children
RECRUITING
Indianapolis
Kansas
Wesley Medical Center
RECRUITING
Wichita
Kentucky
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Norton Children's Hospital
RECRUITING
Louisville
Louisiana
Children's Hospital New Orleans
RECRUITING
New Orleans
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Massachusetts General Hospital Cancer Center
RECRUITING
Boston
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Sinai Hospital of Baltimore
RECRUITING
Baltimore
University of Maryland/Greenebaum Cancer Center
RECRUITING
Baltimore
Maine
Eastern Maine Medical Center
RECRUITING
Bangor
Maine Children's Cancer Program
RECRUITING
Scarborough
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Children's Hospital of Michigan
RECRUITING
Detroit
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITING
Grand Rapids
Bronson Methodist Hospital
RECRUITING
Kalamazoo
Corewell Health Children's
RECRUITING
Royal Oak
Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
RECRUITING
Minneapolis
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
Children's Mercy Hospitals and Clinics
RECRUITING
Kansas City
Mercy Hospital Saint Louis
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
North Carolina
Mission Hospital
RECRUITING
Asheville
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Novant Health Presbyterian Medical Center
RECRUITING
Charlotte
Duke University Medical Center
RECRUITING
Durham
East Carolina University
RECRUITING
Greenville
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Nebraska
Children's Hospital and Medical Center of Omaha
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
RECRUITING
Lebanon
New Jersey
Hackensack University Medical Center
RECRUITING
Hackensack
Morristown Medical Center
RECRUITING
Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
Saint Peter's University Hospital
RECRUITING
New Brunswick
Saint Joseph's Regional Medical Center
RECRUITING
Paterson
New Mexico
University of New Mexico Cancer Center
RECRUITING
Albuquerque
Nevada
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
SUSPENDED
Las Vegas
New York
Albany Medical Center
RECRUITING
Albany
Roswell Park Cancer Institute
RECRUITING
Buffalo
NYU Langone Hospital - Long Island
RECRUITING
Mineola
The Steven and Alexandra Cohen Children's Medical Center of New York
RECRUITING
New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
University of Rochester
RECRUITING
Rochester
State University of New York Upstate Medical University
RECRUITING
Syracuse
Montefiore Medical Center - Moses Campus
RECRUITING
The Bronx
New York Medical College
RECRUITING
Valhalla
Ohio
Children's Hospital Medical Center of Akron
RECRUITING
Akron
Cincinnati Children's Hospital Medical Center
RECRUITING
Cincinnati
Cleveland Clinic Foundation
RECRUITING
Cleveland
Rainbow Babies and Childrens Hospital
RECRUITING
Cleveland
Nationwide Children's Hospital
RECRUITING
Columbus
Dayton Children's Hospital
RECRUITING
Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
RECRUITING
Toledo
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Natalie Warren Bryant Cancer Center at Saint Francis
RECRUITING
Tulsa
Oregon
Legacy Emanuel Children's Hospital
RECRUITING
Portland
Oregon Health and Science University
RECRUITING
Portland
Pennsylvania
Geisinger Medical Center
RECRUITING
Danville
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Saint Christopher's Hospital for Children
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Prisma Health Richland Hospital
RECRUITING
Columbia
BI-LO Charities Children's Cancer Center
RECRUITING
Greenville
South Dakota
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Tennessee
East Tennessee Childrens Hospital
RECRUITING
Knoxville
Saint Jude Children's Research Hospital
RECRUITING
Memphis
The Children's Hospital at TriStar Centennial
RECRUITING
Nashville
Vanderbilt University/Ingram Cancer Center
RECRUITING
Nashville
Texas
Dell Children's Medical Center of Central Texas
RECRUITING
Austin
Driscoll Children's Hospital
RECRUITING
Corpus Christi
Medical City Dallas Hospital
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
El Paso Children's Hospital
RECRUITING
El Paso
Cook Children's Medical Center
RECRUITING
Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
M D Anderson Cancer Center
RECRUITING
Houston
Covenant Children's Hospital
RECRUITING
Lubbock
UMC Cancer Center / UMC Health System
RECRUITING
Lubbock
Children's Hospital of San Antonio
RECRUITING
San Antonio
Methodist Children's Hospital of South Texas
RECRUITING
San Antonio
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Primary Children's Hospital
RECRUITING
Salt Lake City
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Naval Medical Center - Portsmouth
RECRUITING
Portsmouth
Vermont
University of Vermont and State Agricultural College
RECRUITING
Burlington
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
RECRUITING
Spokane
Mary Bridge Children's Hospital and Health Center
RECRUITING
Tacoma
Wisconsin
Saint Vincent Hospital Cancer Center Green Bay
SUSPENDED
Green Bay
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Marshfield Medical Center-Marshfield
SUSPENDED
Marshfield
Children's Hospital of Wisconsin
RECRUITING
Milwaukee
Other Locations
Australia
Royal Children's Hospital
SUSPENDED
Parkville
Perth Children's Hospital
SUSPENDED
Perth
Sydney Children's Hospital
SUSPENDED
Randwick
Queensland Children's Hospital
SUSPENDED
South Brisbane
The Children's Hospital at Westmead
SUSPENDED
Westmead
Canada
Alberta Children's Hospital
SUSPENDED
Calgary
University of Alberta Hospital
SUSPENDED
Edmonton
IWK Health Centre
SUSPENDED
Halifax
McMaster Children's Hospital at Hamilton Health Sciences
SUSPENDED
Hamilton
Children's Hospital
SUSPENDED
London
Centre Hospitalier Universitaire Sainte-Justine
SUSPENDED
Montreal
The Montreal Children's Hospital of the MUHC
SUSPENDED
Montreal
Children's Hospital of Eastern Ontario
SUSPENDED
Ottawa
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
SUSPENDED
Québec
Jim Pattison Children's Hospital
SUSPENDED
Saskatoon
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
SUSPENDED
Sherbrooke
Janeway Child Health Centre
SUSPENDED
St. John's
Hospital for Sick Children
SUSPENDED
Toronto
British Columbia Children's Hospital
SUSPENDED
Vancouver
CancerCare Manitoba
SUSPENDED
Winnipeg
New Zealand
Starship Children's Hospital
SUSPENDED
Grafton
Time Frame
Start Date: 2024-04-19
Estimated Completion Date: 2029-12-31
Participants
Target number of participants: 478
Treatments
Active_comparator: Arm A (SOC treatment)
See detailed description
Experimental: Arm B (Dinutuximab in induction)
See detailed description
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

Similar Clinical Trials