a phase i single-arm clinical study of donor nk cells infusion combined with low-dose interleukin-2 in the treatment of acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation.

Conditions: Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia (AML) Relapse; NK Cell

Summary: this is a single-centre, single-arm, open-label, early clinical study to evaluate the safety, tolerability and preliminary efficacy of donor nk cells injection combined with low-dose interleukin-2 in the treatment of acute myeloid leukemia (aml) relapse after allogeneic hematopoietic stem cell transplantation (allo-hsct).

this is a dose-escalation study of non-genetically modified natural killer cells derived from a healthy donor. the relapsed aml patients after allo-hsct will receive donor nk cells injection s followed by low-dose interleukin-2. no graft-versus-host disease (gvhd) prevention will be conducted before or after infusion. dose-limiting toxicity, incidence of adverse events, disease response and pk/pd will be detected post-infusion.

Eligibility criteria:
inclusion criteria: * 1.age ≥ 18 years old, no gender or race; 2.expected survival period ≥ 3 months; 3.eastern cooperative oncology group (ecog) performance status score of 0 to 2; 4.the diagnosis of aml who received allo-hsct, and met the following criteria: a. diagnostic criteria for relapsed aml: after complete remission (cr), leukemia cells reappeared in peripheral blood or blast cells in bone marrow ≥ 5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; b. minimal residual disease (mrd) positive only or relapse: patient is minimal residual disease (mrd) positive, as assessed on bone marrow aspirate (bma) by multiparameter flow cytometry (mfc) at time of treatment eligibility assessment; c. degree ii and above acute graft-versus-host disease did not occur after transplantation; d. available allogeneic hematopoietic stem cell transplant donors. 5. adequate organ function: a. liver function: alt≤3×uln, ast≤3×uln, total bilirubin≤2×uln; b. coagulation function: international normalized ratio (inr) or activated partial thromboplastin time (aptt) ≤ 1.5×uln; c. renal function: serum creatinine≤1.5×uln or creatinine clearance rate ≥30ml/min; d. cardiac function: left ventricular ejection fraction (lvef) ≥ 45%; 6. women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.; 7. informed consent/assent: all subjects must have the ability to understand and the willingness to sign a written informed consent. exclusion criteria: * 1. central nervous system involved; 2. patients who received the following anti-tumor therapies prior to infusion: a. systemic use of hormones within 3 days prior to infusion (except for patients with inhaled corticosteroids); b. systemic anti-tumor therapy within 2 weeks or within 5 drug half-lives (whichever is shorter); c. radiotherapy within 4 weeks; d. dli within 6 weeks; e. intrathecal injection within 1 week; f. received car-t, car-nk or other modified cell therapy within 6 months; 3. any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: hbv, hcv, hiv, syphilis infection, or active pulmonary tuberculosis. 4. history of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; 5. patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment; 6. women who are pregnant (urine/blood pregnancy test positive) or lactating; 7. suffering from a serious autoimmune disease or immunodeficiency disease; 8. known alcohol dependence or drug dependence; 9. according to the investigator\&#39;s judgment, the patient has other unsuitable grouping conditions.

Keywords: aml relapse allogeneic hematopoietic stem cell transplantation. nk cell