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.
Patient (age from 14 to 25 years) and/or patient's legal representative (age from 0 to 18 years) should provide written informed consent.
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).
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.
Single group
Donor-derived Natural Killer Cell
Biological/VaccineThese 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.
Proportion of patients who received the planned dose of NK cells without adverse reactions grade ≥3 according to CTCAE v5.0
Rate of morphologic bone marrow leukemia-free state
Rate of morphologic bone marrow leukemia-free state on day -4, morphologic complete remission on day +30 (only for patients with chemorefractory acute leukemia).
Rate of MRD-negativity
Cumulative incidence of developing acute graft-versus-host disease
Cumulative incidence of relapse
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