Pilot Study of Combining of Dinutuximab-β With Induction Chemotherapy in Newly Diagnosed High Risk Neuroblastoma
This clinical trial investigates the safety, side effects, and effectiveness of combining an immunotherapy drug called dinutuximab-beta with standard induction chemotherapy for patients newly diagnosed with high-risk neuroblastoma. Dinutuximab-beta is an antibody designed to target specific molecules on the surface of neuroblastoma cells. In this pilot study, enrolled patients will receive dinutuximab-beta as a continuous intravenous infusion alongside a standard 6-cycle induction chemotherapy regimen. The primary goals of this study are to monitor how well patients tolerate the new combination treatment closely and to determine how effectively tumors shrink before patients proceed to the next phase of their standard consolidation therapy.
• 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.