3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma

Study Overview
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Brief Summary
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The purpose of this study is to find out what effects, good and/or bad, the combination of 3F8 and GM-CSF has on the patient and the cancer.

Official Title
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3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma: A Phase II Study

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: 3F8/GM-CSF Immunotherapy Plus 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 in >2nd 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 v34.0) 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/GM-CSF Immunotherapy Plus 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. Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20 mg/m2/day) for all cycles. | Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid<br>* 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 .Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20 mg/m2/day) for all cycles. The patients are in > or = to 2nd CR/VGPR and at high risk for additional relapse. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 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 in second or greater complete or very good partial remission, but at high risk of additional 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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MAB 3F8, GM-CSF, RETINOIC ACID (CIS-9 & 13), 09-160