NCT04385277

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

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 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: I. 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: I. 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: I. 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

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Correlative studies
PROCEDURE	Bone Marrow Aspiration	Undergo BM aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo BM biopsy
PROCEDURE	Computed Tomography	Undergo CT
BIOLOGICAL	Dinutuximab	Given IV
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG-PET
RADIATION	Iobenguane I-123	Undergo 123I-MIBG
DRUG	Irinotecan	Given IV
DRUG	Isotretinoin	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
BIOLOGICAL	Sargramostim	Given SC or IV
DRUG	Temozolomide	Given PO or via enteral tube

Timeline

• Start date: 2020-12-31
• Primary completion: 2023-06-30
• Completion: 2027-09-30
• First posted: 2020-05-12
• Last updated: 2025-10-27
• Results posted: 2024-08-14

Locations

77 sites across 4 countries: United States, Australia, Canada, New Zealand

Regulatory

• FDA-regulated drug study