A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic Acid (RA) Plus GM-CSF in Primary Refractory Neuroblastoma Patients

Study Overview
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Brief Summary
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This is a multicenter, randomized, controlled, open-label study. Patients meeting inclusion/exclusion criteria will be randomized (1:1) to receive two cycles of MAb-3F8 plus GM-CSF or RA plus GM-CSF. Patients who do not respond to their assigned treatment after two cycles may cross-over to receive the alternate treatment. Disease response and safety will be assessed in all patients after cycle 2 and after cycle 4.

Official Title
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A Randomized Study of Monoclonal Antibody 3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Compared to 13-cis-Retinoic Acid Plus GM-CSF in High Risk Stage 4, Primary Refractory Neuroblastoma Patients

Conditions
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Primary Refractory Neuroblastoma

Intervention / Treatment
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* Biological: MAb-3F8
* Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
* Biological: 13-cis-Retinoic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of stage 4 neuroblastoma diagnosed in accordance with the International Neuroblastoma Staging System: either (a) histologic confirmation which may involve immunohistochemical, ultrastructural, and/or cytogenetic studies, or (b) elevated urinary catecholamines plus tumor cells/clumps in the bone marrow. Have evaluable disease or biopsy-proven stable disease in BM by histology or MIBG scan with MIBG-positive disease confined to the bone or bone marrow, plus urine catecholamine results, documented >3 weeks after conventional chemotherapy or >6 weeks after stem-cell transplantation. CT, MRI, or bone scan (if necessary) can be done at 2-3 weeks after conventional chemotherapy confirming that the chemotherapy, radiotherapy, and ABMT are not realistic curative options. Be between 18 months to 13 years old at diagnosis. Have recovered to grade 2 or better toxicities since their prior therapy. Must, if female of childbearing potential, be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at screening and monthly thereafter through the first four cycles of treatment. Have a performance score of at least 60 from Lansky Play Performance Scale if aged up to 16 years or at least 60 from Karnofsky Scale if aged more than 16 years. Have voluntarily agreed to participate. Exclusion Criteria: Have measurable disease ≥ 1 cm assessed by CT or MRI. Have progressive disease (any new lesion; increase of any measurable lesion by >25%; or previous negative marrow positive for tumor). Have disease detectable in CNS (confirmed by CT or MRI of the brain at screening or within 8 weeks of randomization). Be receiving alternative therapy for the treatment of neuroblastoma, e.g. radiotherapy or chemotherapy within 3 weeks of randomization. Require additional therapy (such as radiotherapy) during the first two treatment cycles. Have detectable human anti-mouse antibody titers at screening. Have received prior anti-GD2 investigational therapies. Have a history of allergies to mouse proteins. Have an active infection requiring IV infusion of antibiotics. Be currently receiving long-term chronic treatment with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 13 Years

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM I<br>Intravenous MAb-3F8 plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) | Biological: MAb-3F8<br> <br> Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)<br> <br> |
| Active Comparator: ARM II<br>Oral 13-cis-Retinoic Acid (RA) plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) | Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)<br> <br> Biological: 13-cis-Retinoic Acid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the proportion of patients achieving a complete bone marrow response measured by an absence of histological evidence of bone marrow disease and by MIBG scan after two cycles of treatment. |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A comparison in treatment arms for disease response as measured by CT/MRI scan and urine catecholamines, MIBG extent of disease scores, disease response in cross-over patients. |  | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroblastoma, 3F8, Primary refractory