Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of neuroblastoma as evidenced by one of the following:

- Histological confirmation

- Demonstrates clumps of tumor cells in bone marrow with elevated urinary
catecholamine metabolites

- High-risk refractory or residual disease

- Poorly responding disease, meeting 1 of the following criteria:

- Stable disease or partial response after at least 12 weeks of induction therapy

- Bone marrow containing greater than 100 tumor cells per 100,000 normal cells
after 12 weeks of induction therapy

- Progressive disease during or after therapy

- At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan
since diagnosis and meets disease status criteria

PATIENT CHARACTERISTICS:

Age:

- 1 to 21 (1 to 20 at diagnosis)

Performance status:

- ECOG 0-2

Life expectancy:

- At least 2 months

Hematopoietic:

- Absolute neutrophil count at least 500/mm^3

- Platelet count at least 20,000/mm^3 (transfusion allowed)

- Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

- Bilirubin normal

- AST/ALT no greater than 3 times normal

- No active hepatitis (for HIV-positive patients only)

Renal:

- Glomerular filtration rate or creatinine clearance at least 60 mL/min

- Creatinine less than 1.5 times normal for age

Cardiovascular:

- Ejection fraction at least 55% OR

- Fractional shortening at least 30%

Pulmonary:

- No dyspnea at rest or exercise intolerance

- No requirement for supplemental oxygen

- No active pneumonia (for HIV-positive patients only)

Other:

- No disease of any major organ system that would preclude study participation

- No other active health problems (for HIV-positive patients only)

- No active infections requiring intravenous antivirals, antibiotics, or antifungals

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 3 weeks since prior biologic therapy and recovered

Chemotherapy:

- At least 3 weeks since prior chemotherapy and recovered

- No more than 100 mg/m^2 total dose of prior melphalan

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior total body, whole abdominal, or whole liver irradiation

- No prior therapy with 131 I-MIBG

- At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to
craniospinal or whole lung fields or greater than 50% of bone marrow space) and
recovered

Surgery:

- Prior surgical resection allowed

- Recovered from prior surgery

Other:

- No prior myeloablative therapy

- Prior submyeloablative therapy with peripheral blood stem cell support allowed

- No concurrent antiretrovirals for HIV-positive patients

- Concurrent prolonged antifungal allowed if culture and biopsy negative in suspected
residual radiographic lesions

- No medications that may preclude uptake of 131 I-MIBG for 1 week prior and 2 weeks
after administration of study drugs

- No concurrent hemodialysis