A Phase 2 interventional study of Donor-derived Natural Killer Cell in Acute Myeloid Leukemia, Acute Lymphoblastic T-cell Leukemia and Mixed Phenotype Acute Leukemia, sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology. Recruiting at 1 site in Russia. Open to participants aged 1 Month to 25 Years. Per ClinicalTrials.gov, last updated 2025-12-01.
Sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Phase 2, Interventional, and Treatment
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.
Rationale. In the context of treating children and young adults with high-risk or chemorefractory acute leukemia allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays a crucial role. It is well known, that residual tumor cell volume at the time of allo-HSCT has a significant impact on its outcomes. The antileukemic effect of allo-HSCT in some hematologic malignancies is predominantly mediated by graft-versus-leukemia effect, which is an immune-mediated reaction of engrafted donor hematopoiesis against the recipient's tumor cells. The graft-versus-leukemia effect is generally ascribed to NK-cells conserved within the graft or arising from it early after transplantation.
Primary objective: to evaluate feasibility, safety and to identify the maximum tolerated dose (MTD) of mbIL21 ex vivo-expanded donor-derived NK-cell cells to be infused to children and young adults aged 1 to 25 years with chemorefractory or pre-transplant MRD-positive acute leukemia undergoing allo-HSCT.
Secondary objectives:
FIRST PART OF CONDITIONING: Patients receive fludarabine 40 mg/m2/day IV over 1 hour on days -14 and -13, thiotepa 10 mg/kg/course IV over 1 hour on days -14 and -13 and cyclophosphamide 500 mg/m2 IV over 1 hour on day -14.
SECOND PART OF CONDITIONING: Patients receive fludarabine 40 mg/m2/day IV over 1 hour on days -4 and -3, treosulfan 42 g/m2/course IV over 2 hours on days -4, -3, -2 or busulfan 12 mg/kg/course PO on days -4, -3, -2 or total body irradiation (TBI) 12 Gy/course on days -4, -3, -2.
TRANSPLANT: Patients undergo allogeneic G-CSF mobilized CD3-depleted peripheral blood stem cell transplantation on day 0.
PHARMACOLOGIC GVHD PROPHYLAXIS: Patients receive tocilizumab 8 mg/kg on day -1 and abatacept 10 mg/kg/day IV over 1 hour on days -1, +7, +14 and +28 (the last one - only in case of haploidentical donor).
DONOR NK-CELL INFUSIONS: Each patient is planned to receive two mbIL21 ex vivo-expanded donor-derived NK-cell infusions. Escalating doses of NK-cells (CD3-CD56+) to be infused in the Phase I study as follows:
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.
To be able to receive NK-cell infusion patient must fulfil the following clinical criteria:
DURATION OF THERAPY: 21 day (14 days before HSCT and up to 7 days after HSCT). Follow up during 2 years after HSCT.
CRITERIA FOR PREMATURE STOPPING OF THE STUDY: DLT in 2 patients of expanded cohort with a minimum (Level 0) dose level. DLT is defined as associated with the intervention immune-related adverse event (cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome) grade 3 or higher according to ASTCT criteria.
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's planned enrollment of 15 is below the median of 40 across 3,005 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Federal Research Institute of Pediatric Hematology, Oncology and Immunology is the lead sponsor of 57 studies on the registry; 18 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients with one of the following disease:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biological: Donor-derived Natural Killer Cell
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.
Proportion of patients who received the planned dose of NK cells without adverse reactions grade ≥3 according to CTCAE v5.0
Time frame: 180 days from the last administration of donor NK cells
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).
Time frame: on day -4 before HSCT, and +30 days after HSCT
Rate of MRD-negativity
Time frame: on days -4 before HSCT and +30 days after HSCT
Cumulative incidence of developing acute graft-versus-host disease
Time frame: 180 days from the last administration of donor NK cells
Cumulative incidence of relapse
Time frame: 2 years after allo-HSCT
Cumulative incidence of transplantation-related mortality
Time frame: 100 days and 2 years after allo-HSCT
Probability of engraftment
Time frame: 30 days after allo-HSCT
Overall survival
Time frame: 2 years after allo-HSCT
Plan to share: No
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Federal Research Institute of Pediatric Hematology, Oncology and Immunology