Feasibility and Safety of Donor-derived NK-cell Infusions for Leukemia Relapse Prophylaxis After Hematopoietic Stem Cell Transplantation

NCT07256210 | Recruiting Phase 2

• 1 other identifier: NDGOI-11-2024
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial aims to evaluate the feasibility, adverse reactions and maximum tolerated dose of mbIL21 ex vivo-expanded donor-derived NK-cell infusions before and after haploidentical or matched-related hematopoietic stem cell transplantation in a cohort of pediatric and young adult patients with chemorefractory or minimal residual disease (MRD) positive acute leukemia.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic T-cell Leukemia; Mixed Phenotype Acute Leukemia

Keywords

Natural killer cell therapy; Hematopoietic stem cell transplantation; Leukemia, Acute; Refractory Leukemias; Pre-transplantation MRD-positivity

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who received the planned dose of NK cells without adverse reactions grade ≥3 according to CTCAE v5.0

  180 days from the last administration of donor NK cells

Secondary Outcomes (7)

• Rate of morphologic bone marrow leukemia-free state

  on day -4 before HSCT, and +30 days after HSCT

• Rate of MRD-negativity

  on days -4 before HSCT and +30 days after HSCT

• Cumulative incidence of developing acute graft-versus-host disease

  180 days from the last administration of donor NK cells

• Cumulative incidence of relapse

  2 years after allo-HSCT

• Cumulative incidence of transplantation-related mortality

  100 days and 2 years after allo-HSCT

Study Arms (1)

Biological: Donor-derived Natural Killer Cell Infusions

EXPERIMENTAL

Biological: Donor-derived Natural Killer Cell

Interventions

Donor-derived Natural Killer Cell BIOLOGICAL

These are total doses for two infusions. The first NK-cell infusion on day -12 comprises 2/3 of total NK-cell dose and the second NK-cell infusion approximately on day +5 consists of 1/3 of total NK-cell dose.

Biological: Donor-derived Natural Killer Cell Infusions

Eligibility Criteria

• Age: 1 Month - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient (age from 14 to 25 years) and/or patient's legal representative (age from 0 to 18 years) should provide written informed consent.
• Patients with one of the following disease:
• Acute myeloid leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,01% of bone marrow nucleated cells by flow cytometry);
• Acute T-lymphoblastic leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,1% of bone marrow nucleated cells by flow cytometry);
• Acute mixed phenotype leukemia: a. primary refractory disease (absence of complete remission (CR) after two induction regimens), b. refractory relapse (absence of CR after one salvage regimen), c. MRD-persistence before conditioning (presence of residual leukemic population more than 0,01% of bone marrow nucleated cells by flow cytometry).
• Patient is indicated to receive allo-HSCT according to actual clinical practice.
• Haploidentical or matched related donor was chosen and is available for allo-HSCT (and NK-cell therapy).
• Patient's clinical status: Lansky/Karnowski index ≥50%.
• Kidney function: clearance of endogenous creatinine or glomerular filtration rate according to Schwarz equation ≥50 ml/min/1,73 m2.
• Liver function: total bilirubin ≤3 ULN except for Gilbert's disease, ALT/AST ≤3 ULN.
• Heart function: left ventricular ejection fraction ≥40%.
• Lung function: lung capacity ≥50%, for children who cannot carry out of respiratory function - oxygen saturation during pulse oximetry ≥92% (without supplemental oxygen).
• Life expectancy ≥8 weeks.
• Patients who agree to long-term follow up for up to 2 years.

You may not qualify if:

• Inability to provide or withdrawal of written informed consent.
• Cellular therapy including allo-HSCT within prior 4 months period, absence of active signs of GVHD, sinusoidal obstruction syndrome, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome.
• Active hepatitis B, C or HIV infection.
• Pregnant or lactating women.
• Uncontrolled infection; principal investigator is the final arbiter of this criterion.
• Clinical signs of grade ≥3 CNS disorders (seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, organic brain syndrome, psychosis, coordination or movement disorder).
• Mental illness of the patient or caregivers, making it impossible to realize the essence of the study and compromising compliance with medical appointments and sanitary and hygienic regime.

Sponsors & Collaborators

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

Study Sites (1)

Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology

Moscow, 117997, Russia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Timofei Y Zavidnyi, MD

CONTACT

+79153492188; timofey.zavidnyy@dgoi.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 1, 2025
• Study Start: May 9, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 1, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)