anti-gd2 3f8 monoclonal antibody and gm-csf for high-risk neuroblastoma

Conditions: Neuroblastoma

Summary: the purpose of this study is to be able to supply an experimental combination of drugs called 3f8 and gm-csf (also called sargramostim) to patients with high-risk neuroblastoma who may benefit from treatment.

this treatment uses 3f8/gm-csf and isotretinoin for: group 1 patients are in 1st cr/vgpr; group 2 patients are in a ≥2nd cr/vgpr; and group 3 patients have primary refractory nb in bm. all patients will receive 3f8/gm-csf through 24 months. road map/schema for group 1 (1st cr/vgpr) and group 2 (≥2nd cr/vgpr) patients: cycle 1 3f8 (iv) + gm-csf subcutaneous (sc) (1 wk) 2-4-wk interval cycle 2 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days cycle 3 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days cycle 4 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on cycle 5 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) cycle 6 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval cycle 7 3f8 (iv) + gm-csf (sc) (1 wk) continue with 6-8-wk intervals through 24 months from 1st dose of 3f8. \* assessment of bm status by standard histology road map/schema for group 3 patients (bm positive): the break between end of a cycle of 3f8/gm-csf and start of next cycle is approximately 2-to-4-weeks through 4 cycles after achievement of cr in bm; subsequent breaks are \~6-8 weeks. please see roadmap below for a patient achieving cr in bm after cycle 1. cycle 1 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval\* - bm negative cycle 2 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days cycle 3 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days cycle 4 3f8 (iv) + gm-csf (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days cycle 5 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days cycle 6 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) cycle 7 3f8 (iv) + gm-csf (sc) (1 wk) 6-8-wk interval continue with 6-8-wk intervals through 24 months from 1st dose of 3f8. \* assessment of bm response by standard histology

Eligibility criteria:
inclusion criteria: * diagnosis of nb as defined by international criteria,62 i.e., histopathology (confirmed by the mskcc department of pathology) or bm metastases plus high urine catecholamine levels. * high-risk nb, as defined by risk-related treatment guidelines and the international nb staging system, i.e., stage 4 with (any age) or without (\>18 months) mycnamplification, 63 or mycn-amplified nb other than stage 1.64,65 * patients are in cr/vgpr or have primary refractory nb in bm - i.e., nb resistant to standard therapy, as evidenced by persistence of nb in bm by histology or mibg scan, but all other findings in scans show vgpr. * children and adults are eligible. * signed informed consent indicating awareness of the scheduling and side effects, as well as testing requirements, of this program. exclusion criteria: * existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity \> or = to grade 3, except for grade 3 hematologic toxicity. * progressive disease (pd) * history of allergy to mouse proteins. * active life-threatening infection. * human anti-mouse antibody (hama) titer \>1000 elisa units/ml. * pregnant women * inability to comply with protocol requirements.

Keywords: anti-gd2 3f8 monoclonal antibody oral isotretinoin gm-csf sargramostim 13-260