Study Combining Dinutuximab Beta With Two Chemotherapy Regimens in Neuroblastoma

Overview

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.

This study is a multicenter, open-label, dual-cohort, Phase 1 study of DB combined with each of 2 different induction chemotherapy regimens in 2 cohorts. When the recommended cumulative DB dose level has been defined for each of the chemotherapy regimens, a confirmation cohort of 10 evaluable patients per cohort will be enrolled. The maximum number of patients to be enrolled in the dose escalation and dose confirmation parts of the study combined will be 38 evaluable patients for both induction chemotherapy regimens. For each patient, there will be a screening period of up to 21 days, a treatment period consisting of approximately 126 days (GPOH cohort) or 80 days (rapid COJEC cohort), an end of treatment visit at the end of induction treatment and a post-discontinuation safety visit 30 days after the last administration of DB. Patients will enter the follow up phase after completing the induction treatment. We recommend to follow country/site protocol/guidelines for the management of the patients after the induction treatment (e.g. High Risk-NeuroBLastoma (HR-NBL)-2 study (EudraCT : 2019-001068-31). There are two study periods: The first period lasts until the last patient has completed the end of treatment visit. The analysis of these results will answer the primary endpoint of the study. The planned duration for each patient enrolled is approximately 5 months, and the total study duration is approximately 2 years. The second period lasts until the last patient has completed the follow up. In this period, data for exploratory endpoints are collected. The plan is to report late toxicity (mainly related to the high-dose chemotherapy) when the last patient completed the end of study visit and in a further report the results of 3 and 5 years follow up.