Clinical Trials

Inclusion Criteria:

• Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL1531.
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
  • Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
  • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
  • Age > 547 days regardless of biologic features.
• Patients with INRG stage MS disease with MYCN amplification.
• Patients with INRG stage L2 disease with MYCN amplification.
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M.
• Patients ≥ 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M.
• Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
  • 1 to < 2 years: male = 0.6; female = 0.6;
  • 2 to < 6 years: male = 0.8; female = 0.8;
  • 6 to < 10 years: male = 1; female = 1;
  • 10 to < 13 years: male = 1.2; female = 1.2;
  • 13 to < 16 years: male = 1.5; female = 1.4;
  •  ≥ 16 years: male = 1.7; female = 1.4;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age; and
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45.
• Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram.
• 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.

Exclusion Criteria:

• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial).
• Patients with bone marrow failure syndromesm.
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential. 
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.