ANBL2131: This study is testing how well adding immunotherapy to induction chemotherapy, along with standard of care surgery radiation and stem cell transplantation, works for treating children with newly diagnosed high risk neuroblastomaA Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma

Inclusion

• Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
• ≤ 30 years at the time of initial diagnosis with high-risk disease

• * Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines

  • Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:

    • Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
    • Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
    • Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
    • Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
• Patients must have a body surface area (BSA) ≥ 0.25 m^2

• No prior anti-cancer therapy except as outlined below:

  • Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
  • 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
  • Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
• Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• A serum creatinine based on age/sex as follows:

  • 1 month to < 6 months: Male 0.4 mg/dL and female 0.4mg/dL
  • 6 months to < 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
  • 1 to < 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
  • 2 to < 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
  • 6 to < 10 years: Male 1 mg/dL and female 1 mg/dL
  • 10 to < 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
  • 13 to < 16 years: Male 1.5 mg/dL and female 1.4 mg/dL

  • ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL

    • The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
  • or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 or

  • or a GFR ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)

    • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age

• Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase [ALT]) ≤ 10 x ULN*

  • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

• * Shortening fraction of ≥ 27% by echocardiogram, or

  • Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
• Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:

No known contraindication to 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