Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma

NCT06071897 | Recruiting Phase 3

• 1 other identifier: NCHPOI-2023-08
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroblastoma; Ganglioneuroblastoma

Outcome Measures

Primary Outcomes (2)

• Estimate the Tolerability of the induction chemoimmunotherapy regimen based of courses N5 and N6 with anti-GD2 MAB measured by number of AEs (grade 1-2-3-4-5 measured by CTCAE v.5.0)

  3 years after the start of therapy

• Estimate the toxicity of the induction chemoimmunotherapy regimen based of courses N5 and N6 with anti-GD2 MAB measured by number of AEs (grade 1-2-3-4-5 measured by CTCAE v.5.0)

  3 years after the start of therapy

Secondary Outcomes (4)

• ORR

  At the end of cycle 6 (each cycle is 21 days)

• ORR

  At the end of cycle 6 (each cycle is 21 days)

• OS

  1 and 3 years after completetion of 6th course of induction ( each cycle is 21 days)

• EFS

  1 and 3 years after completetion of 6th course of induction ( each cycle is 21 days)

Study Arms (1)

intervention/treatment

EXPERIMENTAL

\* days of 21 days schedule N5 * Vincristine 1,5 mg/m2 i.v., day 1\* * Etoposide 100 mg/m2 i.v. , days 1-4\* * Cisplatin 100 mg/m2 i.v., days 1-4\* N6 * Vincristine 1,5 mg/m2 i.v. on days 1, 8\* * Dacarbasine 200 mg/m2 i.v., days 1-5\* * Ifosphamide 1500 mg/m2 i.v, days 1-5\* * Doxorubicin 30 mg/m2 i.v, days 6, 7\* N5Q * N5 (see above) * Dinutuximab beta 10 mg/m2 i.v., days 5-9\* 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 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 10 until the ANC is more than 2000 /ml or until counts have recovered for the next cycle of therapy 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.

Drug: monoclonal antibodies GD2

Interventions

monoclonal antibodies GD2 DRUG

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

intervention/treatment

Eligibility Criteria

• Age: 18 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed informed consent
• Verified diagnosis of neuroblastoma or ganglioneuroblastoma (ICD-10 codes C47.3, C47.4, C47.5, C47.6, C47.8, C47.9, C48, C74.1, C74.9, C76.0, C76.1, C76.2, C76.7, C76.8).
• High-risk patients in accordance with the risk stratification of to the GPOH-NB2004 protocol with stage 4 according to the International Neuroblastoma Staging System (INSS) from 18 months of life to 18 years.
• ≥ 70% estimation by Lansky or Karnowski scale at the at the start point of chemoimmunotherapy.
• Life expectancy ≥ 12 weeks from therapy initiation
• No signs of drug-induced neuropathy or neuropathic pain.
• Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity \< 5 values of the upper limit of the norm (VGN).
• Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) \> 60 ml/min/1.73 m2.
• Coagulogram parameters: prothrombin index (PTI) 70-120%, activated partial thromboplastin time (APTT) \< 36 s.
• Absence of clinical signs of heart failure, left ventricular ejection fraction (LVEF) ≥ 55%.
• Assessment of the function of the respiratory system (saturation on the pulse oximeter \> 94% without the use of oxygen, there is no respiratory disturbance at rest), the absence of pathology during chest X-ray.

You may not qualify if:

• Neuroblastoma or ganglioneuroblastoma of the low-risk group or intermediate-risk group, by NB 2004 protocol and disease staging according to INSS (stages 1-3 and 4s without apmplification of MYCN gene, stage 4 in patients under 18 months of age) and high-risk patients with stages 1-3/4s with amplification of MYCN gene.
• Presence in anamnesis of acute intolerance reactions or contraindications to the main chemotherapeutic, immunobiological agents and any concomitant therapy drugs used within the framework of this clinical trial protocol.
• Pregnancy due to the high teratogenic activity and toxicity of drugs used in the clinical trial protocol. A pregnancy test is indicated for patients of childbearing age.

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

Research Institute of Pediatric Hematology, Oncology and Immunology

Moscow, 117997, Russia

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Ganglioneuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Denis Kachanov, MD,PhD

CONTACT

+7 495 664-77-40; Denis.Kachanov@fccho-moscow.ru

Elena Smirnova

CONTACT

+7(985)130-61-03; lena.smirnova@fccho-moscow.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: October 10, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: October 10, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)