Dinutuximab beta combined with two induction chemotherapy regimens for newly diagnosed high-risk neuroblastoma

Phase Ib Study Combining Dinutuximab Beta With Induction Chemotherapy Regimens in Patients With Newly Diagnosed High-risk Neuroblastoma

This will test different doses of dinutuximab beta given with two standard induction chemotherapy regimens in children (18 months to under 18 years) with newly diagnosed high‑risk neuroblastoma to find a safe recommended dose.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Months to 18 Years
• Sex: All
• Sponsor: Princess Maxima Center for Pediatric Oncology (Academic / other)
• Drugs / interventions: dinutuximab, chemotherapy, dinutiximab
• Locations: 1 site (Utrecht, Utrecht)
• Trial ID: NCT06485947 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open‑label Phase 1 dual‑cohort study adding dinutuximab beta to one of two standard induction chemotherapy regimens (GPOH or rapid COJEC) in newly diagnosed high‑risk neuroblastoma. A dose‑escalation phase will determine the recommended Phase II dose or maximum tolerated dose for dinutuximab beta with each chemotherapy backbone, followed by a confirmation cohort of 10 evaluable patients per regimen. Treatment courses differ by regimen (GPOH: 10 mg/m2 × 5 days every 21 days; rapid COJEC: 10 mg/m2 × 3 days every 10 days) and total induction lasts about 126 days (GPOH) or 80 days (rapid COJEC). Up to 38 evaluable patients will be enrolled across escalation and confirmation parts, with safety follow‑up 30 days after the last dinutuximab beta dose and longer clinical follow‑up per local high‑risk neuroblastoma protocols.

Who should consider this trial

Good fit: Children aged 18 months to under 18 years with newly diagnosed Stage M high‑risk neuroblastoma, weight over 12 kg, adequate organ and cardiac function, and no prior cancer‑specific treatment are the intended participants.

Not a fit: Patients who have had prior cancer‑specific treatment, who are under 18 months, weigh 12 kg or less, or who have significant lab or organ dysfunction are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this could identify a tolerable way to integrate dinutuximab beta into induction therapy and potentially improve early disease control for children with high‑risk neuroblastoma.

How similar studies have performed: Anti‑GD2 antibodies such as dinutuximab have improved outcomes in maintenance settings for high‑risk neuroblastoma in previous trials, but adding dinutuximab beta during induction is less established and is being tested here.

Eligibility criteria

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

Where this trial is running

Utrecht, Utrecht

• Princess Maxima center for pediatric oncology — Utrecht, Utrecht, Netherlands (Recruiting)

Study contacts

• Principal investigator: Holger Lode, MD, PhD — Princess Maxima Center for Pediatric Oncology
• Study coordinator: Jorden Veeneman, PhD

Conditions Neuroblastoma