Actively Recruiting

Phase 3
Age: 18Months - 18Years
All Genders
NCT07375563

Chemoimmunotherapy Combined With Autologous NK Cell Therapy for Pediatric Patients With Refractory and Relapsed High-Risk Neuroblastoma and Ganglioneuroblastoma

Led by Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Updated on 2026-01-29

5

Participants Needed

1

Research Sites

156 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Neuroblastoma (NB) is a malignant neoplasm of the sympathetic nervous system, occurring in 1 in 8,000 live births, accounting for 6-10% of all childhood malignant neoplasms and responsible for 12-15% of mortality -, making it the most common and life-threatening extracranial tumor in childhood. Patients with stage 4 high-risk NB is the subgroup with the poorest prognosis. Within this group, two subgroups with an extremely unfavorable disease course are distinguished: patients with a poor response to the induction phase of therapy (refractory disease) and patients with relapsed or progressive disease. Nowadays, 10-15% of patients show a poor end-induction response, whereas achieving a good end-induction response associated with better long-term survival. Improvement of the response to induction therapy may contribute to better treatment outcomes in newly diagnosed high-risk NB patients and can be achieved by intensification of the induction phase to decrease the number of patients with refractory disease. Also intensification of the second-line therapy may contribute to better responses in patients with relapsed and progressive disease. Protocol aimed to overcome heterogeneous tumor drug resistance through the synergistic interaction of cytostatic and immunobiological agents in combination with NK cell therapy. This approach combines cytotoxic agents with anti-GD2 monoclonal antibodies (mAb) to enhance antitumor activity. Cultured, ex vivo-activated autologous NK cells are infused to compensate for effector cell depletion during therapy and to augment antibody-dependent cellular cytotoxicity (ADCC), potentially improving clinical outcomes. This comprehensive approach opens novel prospects for enhancing treatment efficacy in patients with refractory and relapsed high-risk NB. The expected outcomes of this protocol include a significant increase in therapeutic efficacy indicators - objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS), as well as in patient quality of life.

CONDITIONS

Official Title

Chemoimmunotherapy Combined With Autologous NK Cell Therapy for Pediatric Patients With Refractory and Relapsed High-Risk Neuroblastoma and Ganglioneuroblastoma

Who Can Participate

Age: 18Months - 18Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed voluntary informed consent to participate in the clinical trial
  • Histologically verified diagnosis of neuroblastoma or ganglioneuroblastoma
  • Patients stratified to the high-risk group according to the criteria of the German Society of Pediatric Oncology and Hematology (GPOH) - NB 2004
  • Age from 18 months to 18 years
  • Arm A: Refractory disease after induction therapy with poor response (MR, SD), excluding PD
  • Arm B: Relapsed or progressive disease with new tumor lesions or bone marrow involvement
  • Performance status at least 70% (Lansky or Karnofsky scale)
  • Expected life expectancy of at least 12 weeks
  • No signs of drug-induced neuropathy or neuropathic pain
  • Adequate liver function: ALT/AST less than 5 times upper limit of normal
  • Adequate renal function: creatinine clearance or GFR over 60 mL/min/1.73 m2
  • Coagulation parameters within specified ranges (PTI 70-120%, APTT under 36 seconds)
  • No clinical signs of heart failure; LVEF at least 55%
  • Adequate respiratory function with oxygen saturation over 94% on room air and no resting dyspnea
  • Completion of comprehensive tumor assessment
Not Eligible

You will not qualify if you...

  • No signed informed consent
  • Missing pre-treatment assessment results at therapy start
  • Patients classified as low or intermediate risk for neuroblastoma or ganglioneuroblastoma
  • Good response (PR, VGPR, CR) or progressive disease at end of induction phase in intensified induction patients
  • Progressive or relapsed disease involving central nervous system or leptomeningeal involvement
  • History of acute intolerance reactions to key chemotherapy, immunotherapy, or supportive drugs used in this trial
  • Underlying disease complications or comorbidities preventing treatment, including severe type I hypersensitivity
  • Need for medications with known harmful interactions with trial drugs
  • Ultrasound signs of heart failure (LVEF 55% or less), advanced chronic kidney disease (stage III or higher), or acute kidney injury grade I, F, or L
  • Pregnancy; female patients of childbearing potential must have pregnancy testing
  • Mental illness of patient or legal guardians preventing understanding or adherence to study requirements

AI-Screening

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Trial Site Locations

Total: 1 location

1

National medical research center of pediatric haematology, oncology and immulogy named after Dmytriy Rogachyov, Moscow, 117198

Moscow, Russia, 117198

Actively Recruiting

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Research Team

T

Tatyana V Shamanskay, MD, PHD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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