Dinutuximab-beta and Chemotherapy in Newly Diagnosed High-Risk Neuroblastoma

Prior treatment

• Females who are pregnant or breastfeeding (A pregnancy test is required for female patients of childbearing potential).
  • Female patients who are pregnant are ineligible 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.
  • The subject or their partner is planning to conceive
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method during study therapy and for two months after the last dose of (ch14.18/CHO) (dinutuximab-β) are not eligible.

Other illness

• Patients with bone marrow failure syndromes.
• Current requirement for immunosuppressive medications (e.g., tacrolimus, cyclosporine, systemic corticosteroids for reasons other than prevention/treatment of acute allergic reactions or adrenal replacement therapy).

Other

• Participation in other interventional clinical trials within 1 month.
• Inability to obey the trial instructions.

• Must be 1 to 30 years of age at the time of initial diagnosis.
• Must have histological verification of neuroblastoma or ganglioneuroblastoma, OR demonstration of neuroblastoma cells in the bone marrow with elevated urinary VMA at the time of initial diagnosis.
• Must have newly diagnosed high-risk neuroblastoma according to the revised COG NBL risk classifier (version 2), defined as meeting at least ONE of the following:
  • INRG Stage M: MYCN amplification (\> 4-fold increase), OR age 12 to \< 18 months without MYCN amplification but with unfavorable histology/DI = 1/SCA, OR age \> 18 months regardless of biologic features.
  • INRG Stage MS: MYCN amplification, OR age 12 to \< 18 months without MYCN amplification but with unfavorable histology/DI = 1/SCA.
  • INRG Stage L2: MYCN amplification, OR age 18 months to \< 5 years without MYCN amplification but with unfavorable histology, OR age ≥ 5 years without MYCN amplification but with unfavorable histology (undifferentiated or poorly differentiated tumor).
  • INRG Stage L1: Tumor with incomplete resection and MYCN amplification.
  • Patients \> 18 months of age initially diagnosed with INRG Stage L1, L2, or MS who are subsequently upgraded to high-risk disease.
• Must have had no prior systemic therapy, or have only completed the first cycle of induction chemotherapy under the TPOG N2020-HR protocol.
• Must have measurable disease, defined as at least ONE of the following (Note: Patients with elevated VMA only are NOT eligible):
  • Measurable tumor on MRI or CT scan within 3 weeks prior to study entry (≥ 10 mm in at least one dimension) that is MIBG avid or demonstrates increased FDG/FDOPA uptake on PET scan.
  • MIBG or FDG/FDOPA PET scan within 2 weeks prior to study entry with positive uptake at a minimum of one site.
• ECOG Performance Status of 0, 1, or 2.
• Adequate organ function, including:
  • Renal: Creatinine clearance or estimated GFR ≥ 60 mL/min/1.73 m², or serum creatinine ≤ upper limit of normal (ULN) based on age/gender.
  • Liver: Total bilirubin ≤ 1.5 x ULN for age AND SGPT (ALT) ≤ 5.0 x ULN (if liver tumor is present) or ≤ 3.0 x ULN (if no liver tumor).
  • CNS: No clinical or radiological evidence of active CNS disease (well-controlled seizures allowed), and CNS toxicity ≤ Grade 2.
  • Cardiac: Shortening fraction ≥ 27% or Ejection fraction ≥ 50% by ECHO or gated radionuclide study.
  • Pulmonary: No dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry \> 94%.
• Must be enrolled on the TPOG N2020-GD2 protocol with completed informed consent forms, and be willing to proceed to standard therapy of high-risk neuroblastoma with a 10-year follow-up.