Phase Ib Study Combining Dinutuximab Beta With Induction Chemotherapy Regimens in Patients With Newly Diagnosed High-risk Neuroblastoma
The goal of this clinical trial is to to assess the dose level of dinutuximab Beta (DB) when combined with 2 different induction chemotherapy regimens (named GPOH or rapid COJEC) in newly diagnosed high-risk neuroblastoma patients. The main question is: • to assess the safety and tolerability and identifying the recommended phase II dose and/or the maximum tolerable dose of dinutiximab Beta when combined with 2 standard induction chemotherapy regimens Participants will receive: * GPOH + dinutuximab beta infusion duration = 10 mg/m2 × 5 days (50 mg/m2/course) in 21-day treatment intervals. * Rapid COJEC + dinutuximab beta infusion duration = 10 mg/m2 × 3 days (30 mg/m2/course) in 10-day treatment intervals.
• Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria (Appendix 1).
• Age ≥18 months and \<18 years.
• Body weight \>12 kg.
• Alanine transaminase and aspartate aminotransferase \<10 × upper limit of normal (ULN), total bilirubin \<1.5 × ULN based on age specific reference ranges.
• Calculated glomerular filtration rate \> 60 mL/min/1.73 m2 or serum creatinine \<1.5 × ULN corrected for age.
• Shortening fraction (SF) ≥27% and/or left ventricular ejection fraction (LVEF) \>50% as determined by echocardiography or MUGA.
• Able to comply with scheduled follow-up and study procedures.
• Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national law and legislation.