Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

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

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.