Ganglioneuroblastoma, NodularPhase 2NCT04385277
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 Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Ganglioneuroblastoma, Nodular and Neuroblastoma, run by Children's Oncology Group at 77 sites in 4 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Ganglioneuroblastoma, Nodular, Neuroblastoma
- What is being tested?
- Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 77 sitesin 4 countries
- Study dates
- 31 Dec 2020to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 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
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- 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 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
- 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 with moderate or large pericardial effusions are not eligible
- Patients must not have >= grade 2 diarrhea
- 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
- 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
- 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
Trial locations and contacts
77 sites in 4 countries.
77 sites in 4 countries
United States70 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Kaiser Permanente Downey Medical Center
Downey, California, 90242
El Paso Children's Hospital
El Paso, Texas, 79905
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Children's Hospital Los Angeles
Los Angeles, California, 90027
Norton Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Banner Children's at Desert
Mesa, Arizona, 85202
NYU Winthrop Hospital
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
Nemours Children's Hospital
Orlando, Florida, 32827
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
State University of New York Upstate Medical University
Syracuse, New York, 13210
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Australia4 sites
Royal Children's Hospital
Parkville, Victoria, 3052
Perth Children's Hospital
Perth, Western Australia, 6009
Queensland Children's Hospital
South Brisbane, Queensland, 4101
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
New Zealand2 sites
Christchurch Hospital
Christchurch, 8011
Starship Children's Hospital
Grafton, Auckland, 1145
About this study
Official title: 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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the feasibility of administering dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the frontline Post-Consolidation setting in patients with high-risk neuroblastoma who have undergone Induction and Consolidation therapy with tandem high-dose chemotherapy with stem cell rescue (ASCT).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the Post-Consolidation setting.
II. To describe the event-free survival and overall survival of patients who receive dinutuximab in combination with irinotecan and temozolomide, GM-CSF, and isotretinoin in the Post-Consolidation setting.
EXPLORATORY OBJECTIVES:
- To describe the toxicity profiles associated with chemo-immunotherapy in the Post-Consolidation setting according to the type of prior therapy.
II. To describe response to chemo-immunotherapy in the Post-Consolidation setting using the revised International Neuroblastoma Risk Classification (INRC) in patients with evaluable or measurable disease at study entry.
III. To characterize immune and cytokine profiles in patients receiving Post-Consolidation chemo-immunotherapy.
IV. To bank serial blood samples to investigate the relationship between factors related to the tumor, host, and immune environment and clinical outcomes in patients treated with chemo-immunotherapy.
OUTLINE:
Patients receive temozolomide orally (PO) or via enteral tube daily and irinotecan intravenously (IV) over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim subcutaneously (SC) or IV over 2 hours daily on days 6-12, and isotretinoin PO twice daily (BID) on days 8-21. Patients undergo multigated acquisition scan (MUGA) during screening. Patients also undergo magnetic resonance imaging (MRI), or computed tomography (CT), iobenguane I-123 (123I-MIBG), or fludeoxyglucose F-18-positron emission tomography (FDG-PET), bone marrow (BM) aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months.
- Conditions
- Ganglioneuroblastoma, Nodular, Neuroblastoma
- Being tested
- Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Dinutuximab
- Medical subject headings
- Ganglioneuroblastoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Correlative studies
Bone Marrow AspirationProcedure or surgery
Undergo BM aspiration
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo BM biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
DinutuximabBiological
Also called Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18
Given IV
FDG-Positron Emission TomographyProcedure or surgery
Also called FDG, FDG-PET, FDG-PET Imaging
Undergo FDG-PET
Iobenguane I-123Radiation
Also called AdreView, iobenguane I 123
Undergo 123I-MIBG
IrinotecanDrug
Given IV
IsotretinoinDrug
Also called 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Undergo MRI
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
SargramostimBiological
Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine
Given SC or IV
TemozolomideDrug
Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831
Given PO or via enteral tube
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temozolomide, irinotecan, dinutuximab) | Experimental | Patients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Dinutuximab; Procedure: FDG-Positron Emission Tomography; Radiation: Iobenguane I-123; Drug: Irinotecan; Drug: Isotretinoin; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Biological: Sargramostim; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Who Complete 5 Cycles of Dinutuximab + Chemotherapy Without Progressive Disease (PD)
Will be assessed by estimation of the feasibility therapy completion rate together with a 95% Wilson confidence interval (CI).
Measured: Within 30 weeks from the date of first treatment
Secondary outcomes (2)
Event-free Survival (EFS)
EFS Kaplan-Meier estimates will be generated.
Measured: From the time of start of protocol therapy to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed at 1 year.
Overall Survival (OS)
OS Kaplan-Meier estimates will be generated.
Measured: From the time of start of protocol therapy to death, assessed at 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2020
- Study start31 Dec 2020
- Primary completion30 Jun 2023
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ganglioneuroblastoma, NodularStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ami V Desai, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04385277
- Sponsor's protocol ID
- ANBL19P1
- Other IDs
- NCI-2020-02950, ANBL19P1, ANBL19P1, U10CA180886
- Status last verified
- Oct 2025
- First submitted
- 8 May 2020
- Last updated
- 27 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04385277
- Acronym / sponsor ID
- ANBL19P1
- Conditions
- Ganglioneuroblastoma, Nodular, Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 31 Dec 2020 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 12 May 2020 (actual)
- Results
- Posted 14 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To determine the feasibility of administering dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the frontline Post-Consolidation setting in patients with high-risk neuroblastoma who have undergone Induction and Consolidation therapy with tandem high-dose chemotherapy with stem cell rescue (ASCT).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of dinutuximab, GM-CSF, and isotretinoin in combination with irinotecan and temozolomide in the Post-Consolidation setting.
II. To describe the event-free survival and overall survival of patients who receive dinutuximab in combination with irinotecan and temozolomide, GM-CSF, and isotretinoin in the Post-Consolidation setting.
EXPLORATORY OBJECTIVES:
- To describe the toxicity profiles associated with chemo-immunotherapy in the Post-Consolidation setting according to the type of prior therapy.
II. To describe response to chemo-immunotherapy in the Post-Consolidation setting using the revised International Neuroblastoma Risk Classification (INRC) in patients with evaluable or measurable disease at study entry.
III. To characterize immune and cytokine profiles in patients receiving Post-Consolidation chemo-immunotherapy.
IV. To bank serial blood samples to investigate the relationship between factors related to the tumor, host, and immune environment and clinical outcomes in patients treated with chemo-immunotherapy.
OUTLINE:
Patients receive temozolomide orally (PO) or via enteral tube daily and irinotecan intravenously (IV) over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim subcutaneously (SC) or IV over 2 hours daily on days 6-12, and isotretinoin PO twice daily (BID) on days 8-21. Patients undergo multigated acquisition scan (MUGA) during screening. Patients also undergo magnetic resonance imaging (MRI), or computed tomography (CT), iobenguane I-123 (123I-MIBG), or fludeoxyglucose F-18-positron emission tomography (FDG-PET), bone marrow (BM) aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temozolomide, irinotecan, dinutuximab) | Experimental | Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Computed Tomography, Biological: Dinutuximab, Procedure: FDG-Positron Emission Tomography, Radiation: Iobenguane I-123, Drug: Irinotecan, Drug: Isotretinoin, Procedure: Magnetic Resonance Imaging, Procedure: Multigated Acquisition Scan, Biological: Sargramostim, Drug: TemozolomidePatients receive temozolomide PO or via enteral tube daily and irinotecan IV over 90 minutes daily on days 1-5, dinutuximab IV over 10-20 hours daily on days 2-5, sargramostim SC or IV over 2 hours daily on days 6-12, and isotretinoin PO BID on days 8-21. Patients undergo MUGA during screening. Patients also undergo MRI, or CT, I23I-MIBG, or FDG-PET, BM aspiration, and BM biopsy on study. Treatment repeats every 28 days for up to 5 cycles (up to 6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (42 listed)
- 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 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
- 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
Key exclusion criteria (27 listed)
- Patients must not have had progressive disease (PD) per the revised International Neuroblastoma Risk Criteria (INRC) since the initial diagnosis of high-risk neuroblastoma
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionCorrelative studies | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| Bone Marrow AspirationUndergo BM aspiration | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| Bone Marrow BiopsyAlso: Biopsy of Bone Marrow, Biopsy, Bone MarrowUndergo BM biopsy | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| DinutuximabAlso: Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18Given IV | Biological | Treatment (temozolomide, irinotecan, dinutuximab) |
| FDG-Positron Emission TomographyAlso: FDG, FDG-PET, FDG-PET ImagingUndergo FDG-PET | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| Iobenguane I-123Also: AdreView, iobenguane I 123Undergo 123I-MIBG | Radiation | Treatment (temozolomide, irinotecan, dinutuximab) |
| IrinotecanGiven IV | Drug | Treatment (temozolomide, irinotecan, dinutuximab) |
| IsotretinoinAlso: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A AcidGiven PO | Drug | Treatment (temozolomide, irinotecan, dinutuximab) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceUndergo MRI | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| Multigated Acquisition ScanAlso: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool ScanUndergo MUGA | Procedure or surgery | Treatment (temozolomide, irinotecan, dinutuximab) |
| SargramostimAlso: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, ProkineGiven SC or IV | Biological | Treatment (temozolomide, irinotecan, dinutuximab) |
| TemozolomideAlso: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831Given PO or via enteral tube | Drug | Treatment (temozolomide, irinotecan, dinutuximab) |
Primary outcome
Percentage of Patients Who Complete 5 Cycles of Dinutuximab + Chemotherapy Without Progressive Disease (PD)
Time frame: Within 30 weeks from the date of first treatment
Will be assessed by estimation of the feasibility therapy completion rate together with a 95% Wilson confidence interval (CI).
2 secondary outcomes
Event-free Survival (EFS)
Time frame: From the time of start of protocol therapy to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed at 1 year.
Overall Survival (OS)
Time frame: From the time of start of protocol therapy to death, assessed at 1 year.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ami V Desai principal investigator
Children's Oncology Group
77 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Ganglioneuroblastoma, Nodular and Neuroblastoma, run by Children's Oncology Group at 77 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 42 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 77 sites in United States, Australia, New Zealand, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients Who Complete 5 Cycles of Dinutuximab + Chemotherapy Without Progressive Disease (PD) (time frame: Within 30 weeks from the date of first treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2025.