A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy

Inclusion Criteria:

- Diagnosis of neuroblastoma

- High risk at diagnosis

- Meets the International Neuroblastoma Response Criteria (INRC) for complete response,
very good partial response, or partial response for primary site, soft tissue
metastasis, and bone metastasis AND meets the protocol-specified criteria for bone
marrow response

- No more than 10% tumor (of total nucleated cellular content) seen on any
specimen from a bilateral bone marrow aspirate/biopsy

- Patients who have no tumor seen on a prior bone marrow aspirate/biopsy
specimen and then have ≤ 10% tumor seen on any of the bilateral marrow
aspirate/biopsy specimens done at pre-autologous stem cell transplantation
(ASCT) and/or pre-study enrollment evaluation are eligible

- Residual disease by MIBG scan, CT scan, MRI, bone marrow aspiration, or biopsy
allowed

- No progressive disease other than protocol-specified bone marrow response as
described above

- Must have completed therapy that included intensive induction chemotherapy followed
by ASCT and radiotherapy within the past 100 days

- Radiotherapy may be waived for patients who either had a small adrenal mass that
was completely resected up-front or who never had an identifiable primary tumor

- No more than 9 months between the date of starting the first induction
chemotherapy after diagnosis to the date of ASCT (for patients who have
undergone tandem ASCT, this is the date of the first stem cell infusion)

- For patients who were initially diagnosed as non-high risk neuroblastoma,
but later converted (and/or relapsed) to high-risk neuroblastoma, the 9
months restriction should start from the date of induction therapy for
high-risk neuroblastoma (not from the initial induction therapy for
non-high-risk disease) to the date of ASCT

- Lansky performance status (PS) 50-100% (for patients ≤ 16 years of age) OR Karnofsky
PS 50-100% (for patients > 16 years of age)

- Life expectancy ≥ 2 months

- Absolute phagocyte count ≥ 1,000/μL

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine
based on age/gender as follows:

- 0.4 mg/dL (1 to 5 months of age)

- 0.5 mg/dL (6 to 11 months of age)

- 0.6 mg/dL (1 year of age)

- 0.8 mg/dL (2 to 5 years of age)

- 1.0 mg/dL (6 to 9 years of age)

- 1.2 mg/dL (10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT < 5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 55% by radionuclide
angiography

- FEV_1/FVC > 60% by pulmonary function test (if performed)

- No evidence of dyspnea at rest

- No CNS toxicity ≥ grade 2

- Seizure disorder allowed provided patient is on anticonvulsants and it is well
controlled

- Sinusoidal obstruction syndrome allowed provided it is stable or improving

- No other concurrent anticancer therapy

- No prior anti-GD2 antibody therapy

- No prior vaccine therapy for neuroblastoma

- No concurrent pentoxifylline or immunosuppressive drugs (e.g., cyclosporine or
corticosteroids [other than for the treatment of acute allergic reactions to
immunotherapy or treatment of increased intracranial pressure in patients with CNS
tumors])

- No other concurrent cytokines or growth factors