Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
3 other identifiers
interventional
42
3 countries
10
Brief Summary
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. 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. Sargramostim helps the body produce normal infection-fighting white blood cells. These cells also help the dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better than combination chemotherapy alone in treating patients with high-risk neuroblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2019
Longer than P75 for phase_2
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 24, 2018
CompletedFirst Posted
Study publicly available on registry
December 26, 2018
CompletedStudy Start
First participant enrolled
March 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2021
CompletedResults Posted
Study results publicly available
March 14, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2026
CompletedJune 2, 2026
May 1, 2026
2.8 years
December 24, 2018
December 16, 2022
May 13, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Unacceptable Toxicity
Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
Up to the first 5 cycles of treatment
Percentage of Participants Who Are Feasibility "Failure"
Feasibility "failures" were defined as patients that did not receive \>= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
Up to the first 5 cycles of treatment
Secondary Outcomes (3)
Response Rate
Up to the first 5 cycles of treatment
Event-free Survival
Up to 1 year
Overall Survival
Up to 1 year
Other Outcomes (5)
Incidence of Naturally Occurring Anti-glycan Antibodies
Up to 5 years
Incidence of Natural Killer (NK) Receptor NKp30 Isoforms
Up to 5 years
Response of Host Factors, Including Naturally Occurring Anti-glycan Antibodies, KIR/KIR-L Genotyping, Fc Receptor Genotyping, Human Anti-chimeric Antibodies (HACA)
Up to 5 years
- +2 more other outcomes
Study Arms (1)
Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
EXPERIMENTALSee Detailed Description
Interventions
Undergo ASCT
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo EBRT
Given PO
Given IV
Given SC
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.
- Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. The following disease groups are eligible:
- Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
- MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features; OR
- Age \> 547 days regardless of biologic features;
- Patients with INRG stage MS disease with MYCN amplification
- Patients with INRG stage L2 disease with MYCN amplification
- Patients \> 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progress to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M.
- Patients \>= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M.
- Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing as described).
- 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 will also be eligible.
- Patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
- Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/sex as follows:
- Age 1 month to \< 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
- Age 6 months to \< 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
- +13 more criteria
You may not qualify if:
- Patients \>18 months of age with INRG stage L2, MYCN non-amplified, regardless of additional biologic features.
- Patients with bone marrow failure syndromes.
- Patients that are \>= 12 and =\< 18 months of age with INRG stage M and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid \[DNA\] index \> 1) are not eligible.
- Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine, corticosteroids for reasons other than prevention/treatment of allergic reactions, adrenal replacement therapy, etc.) are not eligible.
- Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required 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 during study therapy and for two months after the last dose of ch14.18 (dinutuximab) are not eligible.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Royal Children's Hospital
Parkville, Victoria, 3052, Australia
Starship Children's Hospital
Grafton, Auckland, 1145, New Zealand
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Sara M Federico
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 24, 2018
First Posted
December 26, 2018
Study Start
March 4, 2019
Primary Completion
December 31, 2021
Study Completion
March 31, 2026
Last Updated
June 2, 2026
Results First Posted
March 14, 2023
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page