Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma

Summary: RATIONALE: Monoclonal antibodies, such as monoclonal antibody 3F8, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Combining monoclonal antibody 3F8 with sargramostim may cause a stronger immune response and kill more tumor cells.
  PURPOSE: Phase II trial to study the effectiveness of combining monoclonal antibody 3F8 with sargramostim in treating patients who have neuroblastoma.

Detailed description: OBJECTIVES:
  -  Determine the efficacy of sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk neuroblastoma.
  -  Determine the prognostic impact of minimal residual bone marrow disease on relapse-free survival of patients treated with this regimen.
  -  Compare the effects of short-term (2-hour intravenous) vs prolonged (subcutaneous release) daily GM-CSF on granulocyte activation, in order to establish the optimal route for tumor-cell kill in these patients.
  OUTLINE: This is an open-label study. Patients are stratified according to evaluable disease (yes [primary refractory bone marrow disease] vs no [no evidence of disease]).
  Patients receive sargramostim (GM-CSF) subcutaneously on days -5 to 4 and monoclonal antibody 3F8 IV over 0.5-1.5 hours on days 0-4. Treatment repeats every 3 weeks for 4 courses and then every 8 weeks for up to a total of 24 months in the absence of disease progression or unacceptable toxicity.
  Beginning after 2 courses of GM-CSF and monoclonal antibody 3F8, patients also receive oral isotretinoin twice daily on days 1-14 (when no monoclonal antibody 3F8 is administered). Treatment with isotretinoin repeats approximately every 28 days for 6 courses.
  PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of neuroblastoma by histopathology OR bone marrow metastases and high urine catecholamine levels
  -  Disease must meet risk-related treatment guidelines and any of the following International Neuroblastoma Staging System stages:
  -  Stage 4 with (any age) OR without (> 18 months of age of age) MYCN amplification
  -  MYCN-amplified other than stage 1
  -  No evidence of disease (i.e., in complete response/remission or very good partial response/remission) OR disease resistant to standard therapy (i.e., incomplete response in bone marrow)
  -  No progressive disease or MIBG-avid soft tissue tumor
  PATIENT CHARACTERISTICS:
  -  No existing renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3
  -  No human anti-mouse antibody (HAMA) titer greater than 1,000 Elisa units/mL
  -  No history of allergy to mouse proteins
  -  No active life-threatening infection
  -  Not pregnant
  -  Negative pregnancy test
  PRIOR CONCURRENT THERAPY:
  -  Not specified

Relevance to patient case: not relevant