NCT06071897

Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma

Introduction of Induction Chemoimmunotherapy Regimen for the Treatment of Pediatric Patients With Stage 4 High-risk Neuroblastoma and Ganglioneuroblastoma Older 18 Months

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Academic / Other
• Sex: All
• Age: 18 Months – 18 Years
• Healthy volunteers: Not accepted

Summary

The modern strategy of therapy of high-risk neuroblastoma, stage 4, consists of three phases - induction, consolidation and post- consolidation. Still current approaches demonstrates insufficient levels of ORR (overall response rate), OS (overall survival) and EFS (event free survival). NB-HR-2023 (neuroblastoma high risk) protocol aimed to investigate tolerability and toxicity and potential improvement of ORR, OS and EFS by overcoming of tumor heterogeneous drug resistance using the synergistic interaction of cytostatic and immunobiological agents in the induction. Protocol include the combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB, which is potentially expected to improve outcomes in patients with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage older 18 months. Currently, treatment with combinations of cytostatics with immunobiological agents is limited due to the risk of complications, which, nevertheless, is controlled with proper monitoring and concomitant therapy. Still no data about use of combination of standard chemotherapy (N5 and N6) with ch14.18/CHO MAB (dinutuximab beta) in induction in primary patients with neuroblastoma. Prospective, interventional trial include patients with neuroblastoma and ganglioneuroblastoma, 4th stage of the high-risk group older 18 months, who will receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB. Consolidation and post consolidation chemotherapy courses are not the subjects for analysis. Patients with high-risk neuroblastoma and ganglioneuroblastoma, stage 4, older 18 months who receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB at the Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology Delayed surgery (if needed) will be done after the 4th or 6th course of induction therapy and stem cells apheresis after the 2nd-5th course of induction therapy.

Detailed description

The modern strategy of therapy of high-risk neuroblastoma, stage 4, consists of three phases - induction, consolidation and post- consolidation. Still current approaches demonstrates insufficient levels of ORR (overall response rate), OS (overall survival) and EFS (event free survival). NB-HR-2023 protocol aimed to investigate potential improvement of ORR, OS and EFS by overcoming of tumor heterogeneous drug resistance using the synergistic interaction of cytostatic and immunobiological agents in the induction. Protocol include the combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB, which is potentially expected to improve outcomes. Currently, treatment with combinations of cytostatics with immunobiological agents is limited due to the risk of complications, which, nevertheless, is controlled with proper monitoring and concomitant therapy. Still no data about use of combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB in induction. Main target of this trial is to estimate tolerability and toxicity of combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB Prospective, interventional trial include patients with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage older 18 months, who will receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB. Consolidation and post-consolidation chemotherapy courses are not the subjects for analysis. Patients (n=15) with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage , who receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients to be enrolled should met the eligibility criteria (see below) and will receive the induction therapy: two courses of standard chemotherapy and four courses of combination of anti-GD2 МАB ch14.18/CHO (dinutuximab beta). N5Q cycle: cisplatin (40 mg/m2 per day, IV, in days 1-4) + etoposide (100 mg/m2 per day, IV, days 1-4) + vincristine (1,5 mg/m2 per day, IV, day 1 + dinutuximab beta (10 mg/m2 per day, IV, Days 5-9) N6Q cycle: vincristine (1.5 mg/m2 per day, IV, days 1, 8) + dacarbazine (200 mg/m2 per day, IV, days 1-5) + ifosfamide (1500 mg/m2 per day, IV, days 1-5) + doxorubicin (30 mg/m2 per day, IV, days 6, 7) + dinutuximab beta (10 mg/m2 per day, IV days 6-10). Delayed surgery (if needed) will be done after the 4th or 6th course of induction therapy and stem cells apheresis after the 2nd-5th course of induction therapy. Interim analyses will be carried out in 1, 2 and 3 years from the first patient enrollement. The final analysis with the assessment of the ORR, OS, EFS of patients will be carried out in 1 year and 3 years from the date of inclusion of the last patient in the protocol.

Conditions

• Neuroblastoma
• Ganglioneuroblastoma

Interventions

Type	Name	Description
DRUG	monoclonal antibodies GD2	Main target of this trial is to estimate tolerability and toxicity of combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB N5Q. N5 (see above) Dinutuximab beta 10 mg/m2 i.v., days 5-9\* N6Q. N6 (see above) Dinutuximab beta 10 mg/m2 i.v., days 6-10\* G-CSF (granulocyte colony-stimulating factor) 5 mcg/kg s.c. on day 9 until the ANC is more than 2000 /ml or until counts have recovered for the next cycle of therapy

Timeline

• Start date: 2023-09-01
• Primary completion: 2026-09-01
• Completion: 2029-09-01
• First posted: 2023-10-10
• Last updated: 2023-10-10

Locations

1 site across 1 country: Russia