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

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.

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.