Monoclonal Antibody 3F8 and GM-CSF in Treating Young Patients With High-Risk, Refractory or Relapsed Neuroblastoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as 3F8, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for neuroblastoma. PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody 3F8 when given together with GM-CSF in treating young patients with high-risk, refractory or relapsed neuroblastoma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of monoclonal antibody 3F8 when administered with sargramostim (GM-CSF) in young patients with high-risk, refractory or relapsed neuroblastoma. Assess anti-neuroblastoma effects of this regimen in these patients. OUTLINE: This is an open-label, dose-escalation study of monoclonal antibody 3F8. Patients receive sargramostim (GM-CSF) subcutaneously once daily on days -5 to 11 and monoclonal antibody 3F8 IV over 30 minutes on days 0-4 and 7-11. Treatment repeats every 4-6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of monoclonal antibody 3F8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months for 2 years.

Official Title
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3F8 Antibody Dose Escalation Plus Granulocyte-Macrophage Colony-Stimulating Factor in High-Risk Neuroblastoma: A Phase I Trial

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: monoclonal antibody 3F8
* Biological: sargramostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of NB as defined by international criteria,45 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels. Patients must have refractory or relapsed high-risk NB (including MYCNamplified stage 3/4/4S and MYCN-nonamplified stage 4 >18 months old) resistant to standard therapy. Prior treatment with 3F8 is allowed. Age <21 years. Signed informed consent indicating awareness of the investigational nature of this program. Exclusion Criteria: Existing major organ dysfunction should be grade 2 or less, with the exception of myelosuppression (neutrophil count >500/ul and platelet count >10,000/ul are acceptable), alopecia, hearing loss. Patient cannot be taking antihypertensive medication. History of allergy to mouse proteins. Active life-threatening infection. Human anti-mouse antibody (HAMA) titer >1000 ELISA units/ml. Prior treatment with 3F8 is NOT an exclusion criterion. Inability to comply with protocol requirements. Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is used during the study period.

Ages Eligible for Study
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Maximum Age: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3F8 and GM-CSF<br>One cycle has 5 days of 3F8 treatment. Each day, patients receive GM-CSF subcutaneously  1.5 hr before the start 3F8 infusion. To limit side-effects, patients receive analgesics, antihistamines, and a small dose (IV, over  5 minutes) of heat-modified 3F8. Cycles can be repeated after a 2-4 week interval, up to a total of two cycles. | Biological: monoclonal antibody 3F8<br> <br> Biological: sargramostim<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of monoclonal antibody 3F8 |  | 2 years | 
| Anti-neuroblastoma effects of monoclonal antibody 3F8 and sargramostim (GM-CSF) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma