Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma

Inclusion Criteria:

- Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of
Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine
levels.

- Patients must have high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and
MYCN-nonamplified stage 4 in patients greater than 18 months of age) AND:

- Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy*.

*For NB, standard therapy includes intensive induction chemotherapy, followed by a
variety of consolidation or salvage therapies, depending on response.

- Phase II: Patients must have primary or secondary refractory disease in BM, defined as
morphologic evidence of NB in BM and/or abnormal 123I-MIBG uptake in osteomedullary
sites, OR patients are in ≥2nd CR

- Patients must be older than 1 year of age.

- Prior treatment with murine and humanized 3F8 is allowed. Patients with prior m3F8,
hu3F8, ch14.18 or hu14.18 treatment must have HAHA antibody titer ≤1300 Elisa
units/ml. Human anti-mouse antibody positivity is allowed.

- White blood cell count ≥1000/ul (phase I only)

- Absolute neutrophil count ≥500/ul (phase I only)

- Absolute lymphocyte count ≥500/ul (phase I only)

- Platelet count ≥25,000/ul (phase I only)

- No chemotherapy or immunotherapy for a minimum of three weeks prior to start of hu3F8

- Women of child-bearing potential must be willing to practice an effective method of
birth control while on treatment

- Signed informed consent indicating awareness of the investigational nature of this
program.

Exclusion Criteria:

- Existing major organ dysfunction > grade 2, with the exception of hearing loss and
hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and
platelets).

- Active life-threatening infection.

- Pregnant women or women who are breast-feeding.

- Inability to comply with protocol requirements, including PK studies and genetic
studies (phase I only)

- History of allergy to mouse proteins.

- Human anti-hu3F8 antibody (HAHA) titer >1300 Elisa units/ml.

- History of allergy to GM-CSF