Study of Chemoimmunotherapy for High-Risk Neuroblastoma

Study Overview
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Brief Summary
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The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.

Official Title
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Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma

Conditions
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Neuroblastoma (NB)

Intervention / Treatment
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* Drug: Irinotecan
* Drug: temozolomide
* Biological: Hu3F8
* Drug: GM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of NB as defined by international criteria,.e., histopathology (confirmed by the MSK Department of Pathology) or bone marrow metastases plus high urine catecholamine levels High-risk NB as defined as any of the following: Stage 4 with MYCN amplification (any age) Stage 4 without MYCN amplification (>1.5 years of age) Stage 3 with MYCN amplification (unresectable; any age) Stage 4S with MYCN amplification (any age) Patients fulfill one of the following criteria: Have evidence of soft tissue disease OR If they only have osteomedullary disease at protocol enrollment, they should have: Had previously received Hu3F8+GMCSF therapy AND have had less than a complete response to it OR Had progressed progressive disease after their most recent anti-neuroblastoma therapeutic regimen Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy. Prior treatment with murine and hu3F8 is allowed. Prior treatment with irinotecan or temozolomide is permitted. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody positivity is allowed. Signed informed consent indicating awareness of the investigational nature of this program. Exclusion Criteria: Patients with CR/VGPR disease Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3 except for hearing loss, alopecia, anorexia, nausea, and hypomagnesemia from TPN, which may be grade 3 ANC < 500/uL Platelet count <30K/uL History of allergy to mouse proteins Active life-threatening infection Inability to comply with protocol requirements Women who are pregnant or breast-feeding
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a pilot study of HITS in patients with resistant NB.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)<br>Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF. | Drug: Irinotecan<br>* 50mg/m^2/day IV will be administered from day 1-5<br>Drug: temozolomide<br>* (given concurrently with Irinotecan) 150mg/m^2/day orally<br>Biological: Hu3F8<br>* 2.25mg/kg IV will be administered on days 2, 4, 8 and 10<br>Drug: GM-CSF<br>* 250mcg/m2/day SC will be administered on days 6-10<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | The regimen will be considered safe if there are no toxicities requiring discontinuation of therapy in at least 9/10 patients during the first two cycles. | 2 years | 
| response rate (CR+PR) | Response assessment will be based on the best response over the course of four cycles. Disease response for NB will use the International NB Response Criteria. Patients who withdraw from the study prior to cycle 4 with < partial response will also not be considered evaluable for response and will be replaced. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hu3F8, Irinotecan, Temozolomide, Sargramostim, Chemoimmunotherapy, 17-251