Study Combining Dinutuximab Beta With Two Chemotherapy Regimens in Neuroblastoma (DBPilot)

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: Dinutuximab beta; Drug: chemotherapy treatment called GPOH; Drug: chemotherapy treatment called rapid COJEC

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jorden Veeneman, PhD; Phone Number: +31650173417; Email: trialmanagement@prinsesmaximacentrum.nl
• Study Contact Backup: Name: Paco Bautista, MD, PhD; Phone Number: 0031650006606; Email: f.j.bautista@prinsesmaximacentrum.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Recruiting
    • Princess Máxima Center for Pediatric Oncology
    • Contact: Jorden Veeneman, PhD; Phone Number: 0031650173417; Email: trialmanagement@prinsesmaximacentrum.nl
    • Principal Investigator: Miranda Dierselhuis, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dinutuximab Beta with chemotherapy treatment called GPOH; Dinutuximab Beta will be administered at a fixed daily dose of 10 mg/m2 given as a 24-hour continuous infusion for a scheduled number of days within each treatment cycle of chemotherapy.	Biological: Dinutuximab beta; Combination of immunotherapy with standard chemotherapy; Other Names: Immunotherapy; Drug: chemotherapy treatment called GPOH; chemotherapy treatment called GPOH
Experimental: Dinutuximab Beta with chemotherapy treatment called rapid COJEC; Dinutuximab Beta will be administered at a fixed daily dose of 10 mg/m2 given as a 24-hour continuous infusion for a scheduled number of days within each treatment cycle of chemotherapy.	Biological: Dinutuximab beta; Combination of immunotherapy with standard chemotherapy; Other Names: Immunotherapy; Drug: chemotherapy treatment called rapid COJEC; chemotherapy treatment called rapid COJEC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of dose limiting toxicities (DLTs) associated with the combination of Dinituximab Beta with GPOH chemotherapy regimen	Number of DLT's per dose level of Dinituximab Beta	Within first 63 days of treatment
the incidence of dose limiting toxicities (DLTs) associated with the combination of Dinituximab Beta with rapid COJEC chemotherapy regimen	Number of DLT's per dose level of Dinituximab Beta	Within first 50 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate during after Dinituximab Beta with GPOH chemotherapy regimen	Tumor imaging	126 days
metastatic response rate after Dinituximab Beta with GPOH chemotherapy regimen	Tumor imaging	126 days
overall response rate during after Dinituximab Beta with rapid COJEC chemotherapy regimen	Tumor imaging	80 days
metastatic response rate after Dinituximab Beta with rapid COJEC chemotherapy regimen	Tumor imaging	80 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
event free survival (EFS) from the date of enrollment	exploratory endpoints	5 years
overall survival (OS) from the date of enrollment	exploratory endpoints	5 years

Collaborators and Investigators

• Sponsor: Princess Maxima Center for Pediatric Oncology
• Collaborators: EUSA Pharma, Inc.
• Investigators: Principal Investigator: Holger Lode, MD, PhD, Princess Máxima Center for Pediatric Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma; Antineoplastic Agents; Dinutuximab
• Other Study ID Numbers: SIOPEN-Pilot01.; 2023-509673-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication (CSR)
• IPD Sharing Time Frame: Within 6 months from study end.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No