High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to see if high-dose 3F8 combined with GM-CSF is better than standard dose 3F8 in treating neuroblastoma. Another purpose of the study is to find out what effects, good and/or bad, 3F8 has on cancer. The investigators also want to see if the antibody works against a very small amount of neuroblastoma (minimal residual disease) that is left in the bone marrow.

Official Title
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High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Myeloablative Therapy and Autologous Stem-Cell Transplantation in Patients With High-Risk Neuroblastoma: A Phase II Study

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: 3F8 monoclonal antibody and 13-cis-Retinoic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels. High-risk NB as defined by risk-related treatment guidelines1 and the International NB Staging System,89 i.e., stage 4 with (any age) or without (> or = to 18 months of age) MYCN amplification, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage 4S. The patients are post-stem cell transplantation and in first CR/VGPR, including no measurable MIBG-avid soft tissue tumor assessable for response. Signed informed consent indicating awareness of the investigational nature of this program. Exclusion Criteria: Creatinine > 3.0 mg/dL ALT, AST and Alkaline Phosphatase > 5.0 times the upper limit of normal Bilirubin > 3.0 mg/dL Patients with grade 3 or higher toxicities (using the CTCAE v3.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam. Patients must have normal blood pressure for age. Progressive disease History of allergy to mouse proteins. Active life-threatening infection. Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml. Inability to comply with protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Months

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3F8 monoclonal antibody and 13-cis-Retinoic Acid<br>This phase II, open-label, single arm trial assesses the anti-NB activity of high-dose 3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles. The patients are post-transplant and in 1st complete/very good partial remission (CR/VGPR),89 with no evidence of NB by standard studies, but are at high risk for relapse. | Drug: 3F8 monoclonal antibody and 13-cis-Retinoic Acid<br>* A cycle consists of treatment with 3F8 for 5 days. GMCSF is started 5 days in advance of each 3F8 cycle. The break between end of a cycle of 3F8/GM-CSF and start of next cycle is 2-to-4-weeks through 4 cycles; subsequent breaks are  6-8 weeks. 13-cis-retinoic acid is started after cycle 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Impact of High-dose 3F8/GM-CSF on Relapse-free Survival | in patients who are post-stem-cell transplantation and in first complete or very good partial remission, but at high risk of relapse. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apply Real-time Quantitative RT-PCR to Test the Hypothesis That the Minimal Residual Disease Content of Bone Marrow | after the first treatments with 3F8/GMCSF has significant prognostic impact on relapse-free survival. | 2 years | 
| Monitor Safety of the High-dose Antibody Treatment | to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-158