Clinical Trial Finder

Inclusion Criteria:

• - Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria: - Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (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 deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown.

• - Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: - 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.

• - Patients with 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.

• - Patients >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S.

• - Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per low- or intermediate-risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology.

• - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 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) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age.

• - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age.

• - Shortening fraction >= 27% by echocardiogram or.

• - Ejection fraction >= 50% by radionuclide evaluation.

• - No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.

• - All patients and/or their parents or legal guardians must sign a written informed consent.

• - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion Criteria:

• - Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method.

• - Female patients who are lactating must agree to stop breast-feeding.

• - Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible.

- Patients are not eligible if they have received local radiation which includes any of the following: 1200 centigray (cGy) to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria

PRIMARY OBJECTIVE:

• I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131]) delivered after multi-agent chemotherapy, and b) post-induction busulfan/melphalan (Bu/Mel) consolidation therapy.

SECONDARY OBJECTIVES:

• I. To assess the tolerability of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-induction Bu/Mel consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy.

TERTIARY OBJECTIVES:

• I. To assess the response rate after a regimen of induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy.

• II. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response.

• III. To assess the relative reliability of 123 I-MIBG and fludeoxyglucose F-18 (18FDG)-positron emission tomography (PET) imaging in assessment of tumor activity at diagnosis, and prior to surgical resection.

• IV. To compare detectable tumor burden on the pre-surgical resection radioiodinated-MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan.

• V. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG.

• VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and relate exposure to SOS incidence.

OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy. Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2. Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5. Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive iobenguane I 131 IV over 90-120 minutes on day 1. SURGERY: Patients undergo surgery after course 4 or before consolidation therapy. CONSOLIDATION THERAPY: Within 10-12 weeks from the date of iobenguane I 131 infusion, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0. RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2 dimensional [D], 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease. MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Arms

Experimental: Treatment (131I-MIBG, chemotherapy)

See Detailed Description.

Interventions

Radiation: - 3-Dimensional Conformal Radiation Therapy

Undergo radiotherapy

Procedure: - Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous in vitro-treated peripheral blood stem cell transplantation

Drug: - Busulfan

Given IV

Drug: - Cisplatin

Given IV

Drug: - Cyclophosphamide

Given IV

Drug: - Doxorubicin Hydrochloride

Given IV

Drug: - Etoposide Phosphate

Given IV

Radiation: - External Beam Radiation Therapy

Undergo radiotherapy

Procedure: - In Vitro-Treated Peripheral Blood Stem Cell Transplantation

Undergo autologous in vitro-treated peripheral blood stem cell transplantation

Radiation: - Intensity-Modulated Radiation Therapy

Undergo radiotherapy

Radiation: - Iobenguane I-131

Given IV

Drug: - Isotretinoin

Given PO

Other: - Laboratory Biomarker Analysis

Correlative studies

Drug: - Melphalan

Given IV

Other: - Pharmacological Study

Correlative studies

Other: - Questionnaire Administration

Ancillary studies

Procedure: - Therapeutic Conventional Surgery

Undergo surgery

Drug: - Topotecan Hydrochloride

Given IV

Drug: - Vincristine Sulfate

Given IV