A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG/Irinotecan/Vincristine Followed by Myeloablative Busulfan-Melphalan (Bu-Mel) for Newly Diagnosed High-Risk Neuroblastoma

Inclusion Criteria:

- Diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma by
histology or demonstration of clumps of tumor cells in bone marrow with elevated
urinary catecholamine metabolites meeting 1 of the following staging criteria:

- Newly diagnosed International Neuroblastoma Staging System (INSS) stage 4
disease meeting 1 of the following criteria:

- MYCN amplification (> 4-fold increase in MYCN signals as compared to
reference signals) and age ≥ 365 days regardless of additional biologic
features

- Age > 18 months (> 547 days) regardless of biologic features

- Age 12-18 months (365-547 days) with any of the following 3 unfavorable
biologic features: MYCN amplification, unfavorable pathology, and/or DNA
index = 1, or any biologic feature that is indeterminant, unsatisfactory,
or unknown

- Newly diagnosed INSS stage 3 disease meeting 1 of the following criteria:

- MYCN amplification (> 4-fold increase in MYCN signals as compared to
reference signals) and age ≥ 365 days, regardless of additional biologic
features

- Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN
status

- Newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in
MYCN signals as compared to reference signals) and age ≥ 365 days, regardless of
additional biologic features

- Age ≥ 365 days initially diagnosed with INSS stage 1, 2, or 4S who progressed
(within the past 4 weeks) to a stage 4 without interval chemotherapy

- No patients aged 12-18 months with INSS stage 4 and all 3 favorable biologic
features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1)

- Must be enrolled onto ANBL00B1 biologic study

- Must have ≥ 1 "MIBG-avid target lesion" present on MIBG scan in the past 4 weeks

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

- AST or ALT ≤ 10 times ULN

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

- ≤ 0.6 mg/dL (1 to < 2 years of age)

- ≤ 0.8 mg/dL (2 to < 6 years of age)

- ≤ 1.0 mg/dL (6 to < 10 years of age)

- ≤ 1.2 mg/dL (10 to < 13 years of age)

- ≤ 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- ≤ 1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by radionuclide
evaluation

- Able to tolerate peripheral blood stem cell (PBSC) collection

- No contraindications to PBSC collection including weight, size, or physical
condition that would preclude apheresis

- No prior systemic therapy

- Localized emergency radiotherapy to sites of life-threatening or
function-threatening disease and ≥ 1 measurable lesion is not irradiated

- No more than 1 course of chemotherapy per low- or intermediate-risk
neuroblastoma therapy before determination of MYCN amplification and histology

- No local radiotherapy that includes any of the following:

- 1,200 cGy to more than 33% of both kidneys

- Patient must have ≥ 1 kidney that has not exceeded the dose/volume of
radiation listed

- 1,800 cGy to more than 30% of liver and/or 900cGy to more than 50% of liver

- No other concurrent cancer chemotherapy or immunomodulating agents (including
steroids)