Chemoimmunotherapy with autologous NK‑cell therapy for children with refractory or relapsed high‑risk neuroblastoma and ganglioneuroblastoma

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

This treatment will test whether adding a child's own expanded natural killer (NK) cells to chemoimmunotherapy helps children with refractory or relapsed high‑risk neuroblastoma or ganglioneuroblastoma respond better.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Months to 18 Years
• Sex: All
• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology (other)
• Drugs / interventions: dinutuximab, chemotherapy
• Locations: 1 site (Moscow)
• Trial ID: NCT07375563 on ClinicalTrials.gov

What this trial studies

This Phase 3 protocol enrolls pediatric patients with high‑risk neuroblastoma or ganglioneuroblastoma who have either a poor response to induction (refractory) or have relapsed/progressive disease. Patients undergo peripheral blood collection to grow an autologous NK‑cell product and then receive chemotherapy with irinotecan and temozolomide, combined with dinutuximab beta and infusions of the expanded NK cells on a defined schedule. Arm A (refractory) receives an intensified induction including one IT course followed by four DIT cycles with NK‑cell infusions on Day 7 of each DIT cycle; Arm B (relapsed/progressive) follows a similar plan after NK product manufacture. Cycles are given every 21 days and standard supportive care and follow‑up are provided per protocol.

Who should consider this trial

Good fit: Children aged 18 months to 18 years with histologically confirmed high‑risk neuroblastoma or ganglioneuroblastoma (per GPOH NB2004), who are either refractory after induction (MR/SD) or have relapsed/progressive disease, and have performance status ≥70% and informed consent are eligible.

Not a fit: Patients with rapidly progressive disease during induction, performance status below 70%, uncontrolled infections, inability to provide sufficient autologous cells, or other major contraindications to the protocol therapies are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could increase response rates and extend progression‑free survival in children with refractory or relapsed high‑risk neuroblastoma, potentially improving long‑term outcomes.

How similar studies have performed: Anti‑GD2 immunotherapy (dinutuximab) has improved outcomes in high‑risk neuroblastoma maintenance, and early‑phase studies combining cellular therapies with anti‑GD2 or chemotherapy have shown promise, but autologous NK‑cell combinations remain largely experimental.

Eligibility criteria

Inclusion Criteria:

* 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, aged from 18 months to 18 years, and meeting the following conditions:

  1. Arm A: Refractory disease - patients who have completed the induction phase of therapy (6 cycles of N5/N6) with a poor response to therapy (MR, SD), with the exception of PD
  2. Arm В: Relapsed/progressive disease - patients who develop any new tumor lesions (after having previously achieved СR), or any new tumor lesion; an increase of \>25% in any previously existing measurable lesion; or newly detected bone marrow involvement by NB cells in cases where the bone marrow had previously been free of involvement
* Performance status ≥ 70% (Lansky or Karnofsky scale) at the time of determining the indication for chemoimmunotherapy combined with NK cell therapy.
* Expected life expectancy ≥ 12 weeks.
* No signs of drug-induced neuropathy or neuropathic pain.
* Adequate liver function: alanine aminotransferase (ALT) / aspartate aminotransferase (AST) activity \< 5 × upper limit of normal (ULN).
* Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) \> 60 mL/min/1.73 m².
* Coagulation parameters: prothrombin index (PTI) 70-120%; activated partial thromboplastin time (APTT) \< 36 seconds.
* No clinical signs of heart failure; left ventricular ejection fraction (LVEF) ≥ 55%.
* Adequate respiratory function (oxygen saturation by pulse oximetry \> 94% on room air, no dyspnea at rest), and no pathological findings on chest X-ray.
* Completion of comprehensive assessment to evaluate the extent of the tumor process.

Exclusion Criteria:

* Lack of a signed voluntary informed consent form for participation in the clinical study.
* Absence of comprehensive pre-treatment assessment results at the time of initiation of specific therapy.
* Patients with NBL or ganglioneuroblastoma stratified to low or intermediate-risk group
* Good response (PR, VGPR, CR) or PD at the end of the induction phase of therapy (applicable only to patients receiving therapy within the framework of the intensified induction phase).
* Progressive or relapsed disease with central nervous system involvement and/or leptomeningeal involvement.
* History of acute intolerance reactions to the main chemotherapeutic and immunobiological agents and supportive care drugs used in this clinical trial protocol.
* Presence of complications of the underlying disease and comorbidities that preclude treatment within this protocol, including severe type I hypersensitivity reactions in the medical history.
* Requirement for concomitant medications with known cross pharmacodynamic interactions with the drugs used in this clinical trial protocol.
* Presence of ultrasonographic signs of heart failure (LVEF ≤ 55%), clinical and laboratory signs of chronic kidney disease of stage ≥ III, or kidney injury of grade I, F or L according to the standardized RIFLE criteria for acute kidney injury (an acronym for "risk, injury, failure, loss, end-stage").
* Pregnancy, due to the high teratogenicity and toxicity of the drugs used in this clinical trial protocol. Female patients of childbearing potential are required to undergo pregnancy testing.
* Mental illness of the patient or legal guardians that makes it impossible to understand the nature of the study and compromises adherence to medical prescriptions and sanitary-hygienic requirements.

Where this trial is running

Moscow

• National medical research center of pediatric haematology, oncology and immulogy named after Dmytriy Rogachyov, Moscow, 117198 — Moscow, Russia (RECRUITING)

Study contacts

• Study coordinator: Tatyana V Shamanskay, MD, PHD

Conditions: Neuroblastoma, Ganglioneuroblastoma, Refractory/relapsed neuroblastoma, ganglioneuroblastoma, children, autologous NK cells, chemoimmunotherapy, dinutuximab beta