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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
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

Full criteria on ClinicalTrials.gov

Sites (77)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Royal Children's Hospital
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ParkvilleAustraliaUnknown status
Perth Children's Hospital
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PerthAustraliaUnknown status
Queensland Children's Hospital
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South BrisbaneAustraliaUnknown status
The Children's Hospital at Westmead
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WestmeadAustraliaUnknown status
IWK Health Centre
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HalifaxCanadaUnknown status
Christchurch Hospital
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ChristchurchNew ZealandUnknown status
Starship Children's Hospital
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GraftonNew ZealandUnknown status
Children's Hospital Medical Center of Akron
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AkronUnited StatesUnknown status
Albany Medical Center
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AlbanyUnited StatesUnknown status
C S Mott Children's Hospital
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Ann ArborUnited StatesUnknown status
Children's Healthcare of Atlanta-Egleston
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AtlantaUnited StatesUnknown status
Children's Hospital Colorado
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AuroraUnited StatesUnknown status
Dell Children's Medical Center of Central Texas
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AustinUnited StatesUnknown status
Walter Reed National Military Medical Center
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BethesdaUnited StatesUnknown status
Saint Luke's Cancer Institute - Boise
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BoiseUnited StatesUnknown status
Dana-Farber Cancer Institute
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BostonUnited StatesUnknown status
Carolinas Medical Center/Levine Cancer Institute
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CharlotteUnited StatesUnknown status
University of Chicago Comprehensive Cancer Center
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ChicagoUnited StatesUnknown status
Lurie Children's Hospital-Chicago
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ChicagoUnited StatesUnknown status
University of Illinois
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ChicagoUnited StatesUnknown status
Cincinnati Children's Hospital Medical Center
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CincinnatiUnited StatesUnknown status
Rainbow Babies and Childrens Hospital
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ClevelandUnited StatesUnknown status
Nationwide Children's Hospital
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ColumbusUnited StatesUnknown status
UT Southwestern/Simmons Cancer Center-Dallas
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DallasUnited StatesUnknown status
Medical City Dallas Hospital
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DallasUnited StatesUnknown status
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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DenverUnited StatesUnknown status
Kaiser Permanente Downey Medical Center
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DowneyUnited StatesUnknown status
El Paso Children's Hospital
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El PasoUnited StatesUnknown status
Sanford Broadway Medical Center
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FargoUnited StatesUnknown status
Golisano Children's Hospital of Southwest Florida
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Fort MyersUnited StatesUnknown status
Cook Children's Medical Center
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Fort WorthUnited StatesUnknown status
University of Florida Health Science Center - Gainesville
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GainesvilleUnited StatesUnknown status
Hackensack University Medical Center
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HackensackUnited StatesUnknown status
Connecticut Children's Medical Center
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HartfordUnited StatesUnknown status
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
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HollywoodUnited StatesUnknown status
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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HoustonUnited StatesUnknown status
Riley Hospital for Children
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IndianapolisUnited StatesUnknown status
University of Iowa/Holden Comprehensive Cancer Center
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Iowa CityUnited StatesUnknown status
University of Mississippi Medical Center
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JacksonUnited StatesUnknown status
Nemours Children's Clinic-Jacksonville
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JacksonvilleUnited StatesUnknown status
Children's Mercy Hospitals and Clinics
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Kansas CityUnited StatesUnknown status
Arkansas Children's Hospital
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Little RockUnited StatesUnknown status
Children's Hospital Los Angeles
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Los AngelesUnited StatesUnknown status
Norton Children's Hospital
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LouisvilleUnited StatesUnknown status
Covenant Children's Hospital
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LubbockUnited StatesUnknown status
UMC Cancer Center / UMC Health System
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LubbockUnited StatesUnknown status
Saint Jude Children's Research Hospital
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MemphisUnited StatesUnknown status
Banner Children's at Desert
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MesaUnited StatesUnknown status
NYU Winthrop Hospital
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MineolaUnited StatesUnknown status
Children's Hospitals and Clinics of Minnesota - Minneapolis
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MinneapolisUnited StatesUnknown status
Morristown Medical Center
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MorristownUnited StatesUnknown status
Vanderbilt University/Ingram Cancer Center
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NashvilleUnited StatesUnknown status
The Children's Hospital at TriStar Centennial
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NashvilleUnited StatesUnknown status
Ochsner Medical Center Jefferson
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New OrleansUnited StatesUnknown status
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New YorkUnited StatesUnknown status
Children's Hospital of The King's Daughters
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NorfolkUnited StatesUnknown status
Kaiser Permanente-Oakland
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OaklandUnited StatesUnknown status
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesUnknown status
Children's Hospital and Medical Center of Omaha
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OmahaUnited StatesUnknown status
University of Nebraska Medical Center
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OmahaUnited StatesUnknown status
Children's Hospital of Orange County
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OrangeUnited StatesUnknown status
Nemours Children's Hospital
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OrlandoUnited StatesUnknown status
Saint Jude Midwest Affiliate
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PeoriaUnited StatesUnknown status
Saint Christopher's Hospital for Children
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PhiladelphiaUnited StatesUnknown status
Children's Hospital of Philadelphia
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PhiladelphiaUnited StatesUnknown status
Children's Hospital of Pittsburgh of UPMC
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PittsburghUnited StatesUnknown status
Primary Children's Hospital
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Salt Lake CityUnited StatesUnknown status
Children's Hospital of San Antonio
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San AntonioUnited StatesUnknown status
Methodist Children's Hospital of South Texas
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San AntonioUnited StatesUnknown status
UCSF Medical Center-Mission Bay
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San FranciscoUnited StatesUnknown status
Seattle Children's Hospital
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SeattleUnited StatesUnknown status
Washington University School of Medicine
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St LouisUnited StatesUnknown status
Mercy Hospital Saint Louis
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St LouisUnited StatesUnknown status
State University of New York Upstate Medical University
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SyracuseUnited StatesUnknown status
Montefiore Medical Center - Moses Campus
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The BronxUnited StatesUnknown status
Children's National Medical Center
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Washington D.C.United StatesUnknown status
Alfred I duPont Hospital for Children
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WilmingtonUnited StatesUnknown status

This page is information, not medical advice. Discuss any trial with your doctor.