This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab
work with or without eflornithine in treating patients with neuroblastoma that has come back
(relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy,
such as irinotecan hydrochloride 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. Immunotherapy with monoclonal antibodies, such as dinutuximab, may
induce changes in the body's immune system and may interfere with the ability of tumor cells
to grow and spread. Eflornithine blocks the production of chemicals called polyamines that
are important in the growth of cancer cells. Giving eflornithine with irinotecan
hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with
relapsed or refractory neuroblastoma.
I. To determine whether administration of eflornithine hydrochloride (eflornithine [DFMO]) in
combination with dinutuximab, irinotecan hydrochloride (irinotecan) and temozolomide results
in an improved response rate compared to dinutuximab, irinotecan and temozolomide in patients
with relapsed or refractory neuroblastoma and therefore is a therapeutic regimen worthy of
further testing in patients with newly-diagnosed high-risk neuroblastoma.
I. To compare progression-free survival and overall survival between patients receiving
dinutuximab, irinotecan and temozolomide with and without the addition of DFMO.
II. To define the toxicity profile of DFMO administered with dinutuximab, irinotecan and
I. To characterize the immune and cytokine profiles of patients treated with
DFMO/chemotherapy/dinutuximab combination and correlate with response to therapy.
II. To evaluate GD2 levels in tumor cells from patient bone marrow samples and correlate with
response to therapy.
III. To explore whether the addition of DFMO to the dinutuximab and chemotherapy backbone
affects pain as determined by patient report and opiate usage.
OUTLINE: Patients are randomized to 1 of 2 regimens.
REGIMEN A: Patients receive temozolomide orally (PO), via nasogastric (NG), or gastric (G)
tube on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5,
dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) or IV over
2 hours on days 6-12 of a 21-day cycle. Treatment repeats every 21 days for up to 6 cycles in
the absence of disease progression or unacceptable toxicity.
REGIMEN B: Patients receive eflornithine PO, via NG, or G tube on days -6 to 7 and days 15-21
of cycle 1 and days 1-7 and 15-21 of subsequent cycles, temozolomide PO, via NG, or G tube on
days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5,
dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC or IV over 2 hours on days
6-12. Treatment lasts 28 days for cycle 1 and then every 21 days for subsequent cycles up to
6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and periodically for
High Risk Neuroblastoma, Recurrent Neuroblastoma, Refractory Neuroblastoma
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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