3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow

Study Overview
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Brief Summary
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The purpose of this study is to see 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 Primary Refractory Neuroblastoma in Bone Marrow: 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


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 or MYCN-amplified stage 4S. Patients have primary refractory disease limited to BM, i.e., high-risk NB (defined above) resistant to standard therapy, as evidenced by incomplete response in BM, but no measurable MIBG-avid soft tissue tumor assessable for response and no progressive disease. 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 v 4.0) 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<br>This phase II study of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response in of primary refractory neuroblastoma in bone marrow (i.e., incomplete response to standard treatment). | Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic<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 (20mg/m2/day) for all cycles The patients have primary refractory BM disease. Protocol treatment is through 24 months. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started no later than after cycle 4 (i.e., after response is scored), but sooner if CR is achieved after cycles 1, 2, or 3, or if early HAMA develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the Activity of High-dose 3F8/GM-CSF | against persistent neuroblastoma in bone marrow of patients who have no other evidence of disease by standard studies. | 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 progression-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), 09-161