Study Combining Dinutuximab Beta With Two Chemotherapy Regimens in Neuroblastoma

Summary

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.

Eligibility

Inclusion Criteria:

1. Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria (Appendix 1).
2. Age ≥18 months and \<18 years.
3. Body weight \>12 kg.
4. Alanine transaminase and aspartate aminotransferase \<10 × upper limit of normal (ULN), total bilirubin \<1.5 × ULN based on age specific reference ranges.
5. Calculated glomerular filtration rate \> 60 mL/min/1.73 m2 or serum creatinine \<1.5 × ULN corrected for age.
6. Shortening fraction (SF) ≥27% and/or left ventricular ejection fraction (LVEF) \>50% as determined by echocardiography or MUGA.
7. Able to comply with scheduled follow-up and study procedures.
8. 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.

Exclusion Criteria:

1. Previous cancer-specific treatment for neuroblastoma.
2. Current use of a prohibited medication or requires any of these medications during the study:

   1. Treatment with corticosteroids is not allowed within 2 weeks prior to the first block of chemotherapy and until 1 week after the last treatment course with dinutuximab beta, except for life-threatening conditions.
   2. Vaccinations (including seasonal influenza) are not allowed during administration of dinutuximab beta and until 10 weeks after last treatment course.
   3. Concomitant use of intravenous (IV) immunoglobulins is not allowed.
   4. Concomitant use of cardioprotectant dexrazoxane is not allowed.
3. Pregnancy or positive pregnancy test in females of childbearing potential.
4. Breast feeding.
5. Sexually active participants not willing to use highly effective contraceptive method
6. Major surgery within 21 days prior to the first treatment dose
7. History or documented evidence of severe acute or chronic infection or infectious illness requiring parenteral therapy unless fully healed
8. Patients with spinal cord involvement
9. Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug
10. Have a known immediate or delayed hypersensitivity reaction to study drugs

Conditions2

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