NCT04385277Active, not recruitingPhase 2
Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL)
A Pilot Study of Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide in the Post-Consolidation Setting for High-Risk Neuroblastoma
Source: ClinicalTrials.gov · Last updated 27 Oct 2025
Brief summary (registry, in English)
This phase II trial studies if dinutuximab, GM-CSF, isotretinoin in combination with irinotecan, and temozolomide (chemo-immunotherapy) can be given safely to patients with high-risk neuroblastoma after Consolidation therapy (which usually consists of two autologous stem cell transplants and radiation) who have not experienced worsening or recurrence of their disease. Dinutuximab represents a kind of cancer therapy called immunotherapy. Unlike chemotherapy and radiation, dinutuximab targets the cancer cells without destroying nearby healthy cells. Sargramostim helps the body produce normal infection-fighting white blood cells. Isotretinoin helps the neuroblastoma cells become more mature. These 3 drugs (standard immunotherapy) are already given to patients with high-risk neuroblastoma after Consolidation because they have been proven to be beneficial in this setting. Chemotherapy drugs, such as irinotecan and temozolomide, 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. They may also affect how well immunotherapy works on neuroblastoma cells. Giving chemo-immunotherapy after intensive therapy may work better in treating patients with high-risk neuroblastoma compared to standard immunotherapy.
- Status (registry)
- Active, not recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 41 (actual)
- First submitted
- 8 May 2020
- Start date
- 31 Dec 2020
- Primary completion date
- 30 Jun 2023
- Lead sponsor
- Children's Oncology Group
- Diseases
- Neuroblastoma, Childhood cancers
- NCT number
- NCT04385277
What you commit to
- Study type: Interventional · Phase 2
- Participants enrolled: 41
- From 31 Dec 2020 to the primary completion date, 30 Jun 2023
- 77 sites in 4 countries
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Patients may not have received additional systemic cancer-directed therapy following completion of the last planned high-dose chemotherapy with ASCT prior to enrollment on this trial
- Patients may not have received iodine-131 (131I)-metaiodobenzylguanidine (MIBG) therapy at any time prior to enrollment on this trial
- Patients who received single (rather than tandem) high-dose chemotherapy with ASCT are excluded
- Patients cannot be receiving other ongoing anticancer therapy
- Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment
- Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions
- Note: The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency
- Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) are not eligible. However, prior or planned concomitant treatment with eculizumab is permitted (e.g., treatment of TA-TMA)
- Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment
- Note: Patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam are eligible
- Patients must not have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
- 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 for female patients of childbearing potential
Other illness
- Patients must not have had progressive disease (PD) per the revised International Neuroblastoma Risk Criteria (INRC) since the initial diagnosis of high-risk neuroblastoma
- Exception: Progressive disease within the first 2 cycles of Induction chemotherapy consisting of cyclophosphamide and topotecan is allowed. Patients with progression subsequent to initial cyclophosphamide and topotecan cycles are excluded
- Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma
- Patients with symptoms of congestive heart failure are not eligible
- Patients must not have uncontrolled infection
- Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible
- Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Other
- Patients who were enrolled onto ANBL1531 AND underwent arm assignment are not eligible. Patients who enrolled onto ANBL1531 who declined second consent may be eligible for ANBL19P1 if all other criteria are met
- Patients enrolled onto ANBL17P1 are not eligible
- Patients with moderate or large pericardial effusions are not eligible
- Patients must not have \>= grade 2 diarrhea
- 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
Who the study is looking for
- Patients must be \< 31 years of age at the time of enrollment.
- 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 at the time of diagnosis) and have been designated as having high-risk disease based on Children's Oncology Group (COG) risk classification. The following disease groups are eligible:
- Patients with International Neuroblastoma Risk Group (INRG) Stage M disease with any of the following features:
- MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
- Age \> 547 days at the time of diagnosis regardless of biologic features; OR
- Age 365-547 days at the time of diagnosis with tumors with unfavorable histology and/or deoxyribonucleic acid (DNA) index = 1
- Patients with INRG Stage MS disease with MYCN amplification
- Patients with INRG Stage L2 disease with either of the following features:
- MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
- Age \> 547 days at the time of diagnosis with MYCN non-amplified tumors with unfavorable histology
- Note: Patients observed or patients 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 criteria will also be eligible
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years
- Prior therapy
- All patients must have completed high-risk Induction therapy with 4-6 cycles of chemotherapy
- After completion of Induction therapy, patients may have received no more than 4 cycles of bridging chemotherapy or chemo-immunotherapy prior to ASCT
- Patients cannot have previously progressed on immunotherapy with dinutuximab or other anti-GD2 monoclonal antibody
- All patients must have had undergone surgical resection of their primary tumor as part of frontline therapy. Exceptions to this requirement include patients who had a complete response to Induction chemotherapy, patients with no identifiable primary tumor, and patients for whom the institutional surgical team determined that potential risks outweighed potential benefits of resection
- All patients must have undergone tandem high-dose chemotherapy with ASCT as part of Consolidation
- Patients must enroll between day +56 and day +200 from the peripheral blood stem cell (PBSC) infusion following the last dose of high-dose chemotherapy during Consolidation
- All patients must have undergone external beam radiation therapy. Exceptions to this requirement include patients who had no identifiable primary tumor and no persistent metastatic disease at the end of Induction. For patients who received radiotherapy, at least 7 days must have elapsed between completion of radiotherapy and enrollment on this study
- Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor
- Peripheral absolute neutrophil count (ANC) \>= 750/uL
- Platelet count \>= 50,000/uL (transfusion independent for \>= 7 days)
- 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:
- Age: Maximum Serum Creatinine (mg/dL)
- 6 months to \< 1 year: 0.5 (male and female)
- 1 to \< 2 years: 0.6 (male and female)
- 2 to \< 6 years: 0.8 (male and female)
- 6 to \< 10 years: 1 (male and female)
- 10 to \< 13 years: 1.2 (male and female)
- 13 to \< 16 years: 1.5 (male), 1.4 (female)
- \>= 16 years: 1.7 (male), 1.4 (female)
- Note: Patients with history of transplant associated-thrombotic microangiopathy (TA-TMA) must have a creatinine clearance or radioisotope GFR at baseline to assess renal function and must meet the above criteria
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5.0 x ULN for age (=\< 225 U/L)
- 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
- Absence of dyspnea at rest
- If pulmonary function tests (PFTs) are performed, forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) must be \> 60%
- No clinical evidence of active central nervous system (CNS) disease at the time of study enrollment
- Patients with seizure disorder may be enrolled if on non-enzyme-inducing anticonvulsants and well controlled
- CNS toxicity from prior therapy =\< grade 2
Age in the registry: - to 30 years · Sex: All · Does not accept healthy volunteers
Sites (77)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Royal Children's Hospital Coordinator of this site? Confirm its status | Parkville | Australia | Unknown status |
| Perth Children's Hospital Coordinator of this site? Confirm its status | Perth | Australia | Unknown status |
| Queensland Children's Hospital Coordinator of this site? Confirm its status | South Brisbane | Australia | Unknown status |
| The Children's Hospital at Westmead Coordinator of this site? Confirm its status | Westmead | Australia | Unknown status |
| IWK Health Centre Coordinator of this site? Confirm its status | Halifax | Canada | Unknown status |
| Christchurch Hospital Coordinator of this site? Confirm its status | Christchurch | New Zealand | Unknown status |
| Starship Children's Hospital Coordinator of this site? Confirm its status | Grafton | New Zealand | Unknown status |
| Children's Hospital Medical Center of Akron Coordinator of this site? Confirm its status | Akron | United States | Unknown status |
| Albany Medical Center Coordinator of this site? Confirm its status | Albany | United States | Unknown status |
| C S Mott Children's Hospital Coordinator of this site? Confirm its status | Ann Arbor | United States | Unknown status |
| Children's Healthcare of Atlanta-Egleston Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Children's Hospital Colorado Coordinator of this site? Confirm its status | Aurora | United States | Unknown status |
| Dell Children's Medical Center of Central Texas Coordinator of this site? Confirm its status | Austin | United States | Unknown status |
| Walter Reed National Military Medical Center Coordinator of this site? Confirm its status | Bethesda | United States | Unknown status |
| Saint Luke's Cancer Institute - Boise Coordinator of this site? Confirm its status | Boise | United States | Unknown status |
| Dana-Farber Cancer Institute Coordinator of this site? Confirm its status | Boston | United States | Unknown status |
| Carolinas Medical Center/Levine Cancer Institute Coordinator of this site? Confirm its status | Charlotte | United States | Unknown status |
| University of Chicago Comprehensive Cancer Center Coordinator of this site? Confirm its status | Chicago | United States | Unknown status |
| Lurie Children's Hospital-Chicago Coordinator of this site? Confirm its status | Chicago | United States | Unknown status |
| University of Illinois Coordinator of this site? Confirm its status | Chicago | United States | Unknown status |
| Cincinnati Children's Hospital Medical Center Coordinator of this site? Confirm its status | Cincinnati | United States | Unknown status |
| Rainbow Babies and Childrens Hospital Coordinator of this site? Confirm its status | Cleveland | United States | Unknown status |
| Nationwide Children's Hospital Coordinator of this site? Confirm its status | Columbus | United States | Unknown status |
| UT Southwestern/Simmons Cancer Center-Dallas Coordinator of this site? Confirm its status | Dallas | United States | Unknown status |
| Medical City Dallas Hospital Coordinator of this site? Confirm its status | Dallas | United States | Unknown status |
| Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Coordinator of this site? Confirm its status | Denver | United States | Unknown status |
| Kaiser Permanente Downey Medical Center Coordinator of this site? Confirm its status | Downey | United States | Unknown status |
| El Paso Children's Hospital Coordinator of this site? Confirm its status | El Paso | United States | Unknown status |
| Sanford Broadway Medical Center Coordinator of this site? Confirm its status | Fargo | United States | Unknown status |
| Golisano Children's Hospital of Southwest Florida Coordinator of this site? Confirm its status | Fort Myers | United States | Unknown status |
| Cook Children's Medical Center Coordinator of this site? Confirm its status | Fort Worth | United States | Unknown status |
| University of Florida Health Science Center - Gainesville Coordinator of this site? Confirm its status | Gainesville | United States | Unknown status |
| Hackensack University Medical Center Coordinator of this site? Confirm its status | Hackensack | United States | Unknown status |
| Connecticut Children's Medical Center Coordinator of this site? Confirm its status | Hartford | United States | Unknown status |
| Memorial Regional Hospital/Joe DiMaggio Children's Hospital Coordinator of this site? Confirm its status | Hollywood | United States | Unknown status |
| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Coordinator of this site? Confirm its status | Houston | United States | Unknown status |
| Riley Hospital for Children Coordinator of this site? Confirm its status | Indianapolis | United States | Unknown status |
| University of Iowa/Holden Comprehensive Cancer Center Coordinator of this site? Confirm its status | Iowa City | United States | Unknown status |
| University of Mississippi Medical Center Coordinator of this site? Confirm its status | Jackson | United States | Unknown status |
| Nemours Children's Clinic-Jacksonville Coordinator of this site? Confirm its status | Jacksonville | United States | Unknown status |
| Children's Mercy Hospitals and Clinics Coordinator of this site? Confirm its status | Kansas City | United States | Unknown status |
| Arkansas Children's Hospital Coordinator of this site? Confirm its status | Little Rock | United States | Unknown status |
| Children's Hospital Los Angeles Coordinator of this site? Confirm its status | Los Angeles | United States | Unknown status |
| Norton Children's Hospital Coordinator of this site? Confirm its status | Louisville | United States | Unknown status |
| Covenant Children's Hospital Coordinator of this site? Confirm its status | Lubbock | United States | Unknown status |
| UMC Cancer Center / UMC Health System Coordinator of this site? Confirm its status | Lubbock | United States | Unknown status |
| Saint Jude Children's Research Hospital Coordinator of this site? Confirm its status | Memphis | United States | Unknown status |
| Banner Children's at Desert Coordinator of this site? Confirm its status | Mesa | United States | Unknown status |
| NYU Winthrop Hospital Coordinator of this site? Confirm its status | Mineola | United States | Unknown status |
| Children's Hospitals and Clinics of Minnesota - Minneapolis Coordinator of this site? Confirm its status | Minneapolis | United States | Unknown status |
| Morristown Medical Center Coordinator of this site? Confirm its status | Morristown | United States | Unknown status |
| Vanderbilt University/Ingram Cancer Center Coordinator of this site? Confirm its status | Nashville | United States | Unknown status |
| The Children's Hospital at TriStar Centennial Coordinator of this site? Confirm its status | Nashville | United States | Unknown status |
| Ochsner Medical Center Jefferson Coordinator of this site? Confirm its status | New Orleans | United States | Unknown status |
| NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center Coordinator of this site? Confirm its status | New York | United States | Unknown status |
| Children's Hospital of The King's Daughters Coordinator of this site? Confirm its status | Norfolk | United States | Unknown status |
| Kaiser Permanente-Oakland Coordinator of this site? Confirm its status | Oakland | United States | Unknown status |
| University of Oklahoma Health Sciences Center Coordinator of this site? Confirm its status | Oklahoma City | United States | Unknown status |
| Children's Hospital and Medical Center of Omaha Coordinator of this site? Confirm its status | Omaha | United States | Unknown status |
| University of Nebraska Medical Center Coordinator of this site? Confirm its status | Omaha | United States | Unknown status |
| Children's Hospital of Orange County Coordinator of this site? Confirm its status | Orange | United States | Unknown status |
| Nemours Children's Hospital Coordinator of this site? Confirm its status | Orlando | United States | Unknown status |
| Saint Jude Midwest Affiliate Coordinator of this site? Confirm its status | Peoria | United States | Unknown status |
| Saint Christopher's Hospital for Children Coordinator of this site? Confirm its status | Philadelphia | United States | Unknown status |
| Children's Hospital of Philadelphia Coordinator of this site? Confirm its status | Philadelphia | United States | Unknown status |
| Children's Hospital of Pittsburgh of UPMC Coordinator of this site? Confirm its status | Pittsburgh | United States | Unknown status |
| Primary Children's Hospital Coordinator of this site? Confirm its status | Salt Lake City | United States | Unknown status |
| Children's Hospital of San Antonio Coordinator of this site? Confirm its status | San Antonio | United States | Unknown status |
| Methodist Children's Hospital of South Texas Coordinator of this site? Confirm its status | San Antonio | United States | Unknown status |
| UCSF Medical Center-Mission Bay Coordinator of this site? Confirm its status | San Francisco | United States | Unknown status |
| Seattle Children's Hospital Coordinator of this site? Confirm its status | Seattle | United States | Unknown status |
| Washington University School of Medicine Coordinator of this site? Confirm its status | St Louis | United States | Unknown status |
| Mercy Hospital Saint Louis Coordinator of this site? Confirm its status | St Louis | United States | Unknown status |
| State University of New York Upstate Medical University Coordinator of this site? Confirm its status | Syracuse | United States | Unknown status |
| Montefiore Medical Center - Moses Campus Coordinator of this site? Confirm its status | The Bronx | United States | Unknown status |
| Children's National Medical Center Coordinator of this site? Confirm its status | Washington D.C. | United States | Unknown status |
| Alfred I duPont Hospital for Children Coordinator of this site? Confirm its status | Wilmington | United States | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.