Donor-derived NK-cell infusions to prevent leukemia relapse after stem cell transplant

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase I/II program that begins with a 3+3 dose-escalation (phase I) to identify the maximum tolerated dose of mbIL21-expanded donor NK cells and proceeds to a phase II cohort. Donor-derived NK cells are expanded ex vivo with mbIL21 and infused around the time of allogeneic hematopoietic stem cell transplantation (split conditioning regimen) with two planned NK-cell infusions. The trial enrolls pediatric and young adult patients with chemorefractory or pre-transplant MRD-positive acute myeloid leukemia, T-lymphoblastic leukemia, or mixed phenotype acute leukemia who receive haploidentical or matched-related grafts. Primary endpoints are feasibility, safety, and MTD; secondary endpoints include short-term disease response, lymphocyte subset reconstitution, and transplant outcomes.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Patient (age from 14 to 25 years) and/or patient's legal representative (age from 0 to 18 years) should provide written informed consent.
2. 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).
3. Patient is indicated to receive allo-HSCT according to actual clinical practice.
4. Haploidentical or matched related donor was chosen and is available for allo-HSCT (and NK-cell therapy).
5. Patient's clinical status: Lansky/Karnowski index ≥50%.
6. Kidney function: clearance of endogenous creatinine or glomerular filtration rate according to Schwarz equation ≥50 ml/min/1,73 m2.
7. Liver function: total bilirubin ≤3 ULN except for Gilbert's disease, ALT/AST ≤3 ULN.
8. Heart function: left ventricular ejection fraction ≥40%.
9. Lung function: lung capacity ≥50%, for children who cannot carry out of respiratory function - oxygen saturation during pulse oximetry ≥92% (without supplemental oxygen).
10. Life expectancy ≥8 weeks.
11. Patients who agree to long-term follow up for up to 2 years.

Exclusion Criteria:

1. Inability to provide or withdrawal of written informed consent.
2. 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.
3. Active hepatitis B, C or HIV infection.
4. Pregnant or lactating women.
5. Uncontrolled infection; principal investigator is the final arbiter of this criterion.
6. 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).
7. 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.

Where it's running

• Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
  Moscow, Russia Recruiting

Study contacts

• Study coordinator: Timofei Y Zavidnyi, MD
• Email: timofey.zavidnyy@dgoi.ru
• Phone: +79153492188

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.