Treatment With Dinutuximab, Sargramostim (GM-CSF), and Isotretinoin in Combination With Irinotecan and Temozolomide After Intensive Therapy for People With High-Risk Neuroblastoma (NBL)
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|ClinicalTrials.gov Identifier: NCT04385277|
Recruitment Status : Recruiting
First Posted : May 12, 2020
Last Update Posted : March 22, 2021
|Condition or disease||Intervention/treatment||Phase|
|Ganglioneuroblastoma, Nodular High Risk Neuroblastoma||Biological: Dinutuximab Drug: Irinotecan Drug: Isotretinoin Biological: Sargramostim Drug: Temozolomide||Phase 2|
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).
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 isotretinoinin the Post-Consolidation setting.
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.
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. 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||November 30, 2020|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Treatment (temozolomide, irinotecan, dinutuximab)
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. Treatment repeats every 28 days for 5 cycles (6 cycles for isotretinoin only) in the absence of disease progression or unacceptable toxicity.
Given SC or IV
Given PO or via enteral tube
- Proportion 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).
- 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 up to 60 months ]EFS Kaplan-Meier curves and estimates will be generated.
- Overall survival (OS) [ Time Frame: From the time of start of protocol therapy to death, assessed up to 60 months ]OS Kaplan-Meier curves and estimates will be generated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04385277
|Principal Investigator:||Ami V Desai||Children's Oncology Group|