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.

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.

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.

Inclusion Criteria:

• Age ≥ 18 years old,;
• Expected survival period ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
• 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.

-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%;

• Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.;
• Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Central nervous system involved;
• 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;

• 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.
• History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
• Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment;
• Women who are pregnant (urine/blood pregnancy test positive) or lactating;
• Suffering from a serious autoimmune disease or immunodeficiency disease;
• Known alcohol dependence or drug dependence;
• According to the investigator's judgment, the patient has other unsuitable grouping conditions.