off-the-shelf cd123 car-nk for r/r aml

Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Summary: this is a single-centre, single-arm, open-label, first-in-human (fih) study to evaluate the safety, tolerability and preliminary efficacy of universal off-the-shelf car-nk cells targeted cd123 (jd123 injection) in the treatment of refractory or relapsed cd123-positive acute myeloid leukemia (aml).

this is a dose-escalation study of cd123-targeted chimeric antigen receptor modified natural killer cells (car-nk) derived from a healthy donor. the relapsed/refractory aml patients will receive fc (f, fludarabine, c, cyclophosphamide) chemotherapy followed by infusion of jd123 injections. 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 with bone marrow biopsy, immunohistochemistry or flow cytometry definitively positive for cd123 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. diagnostic criteria for refractory aml: naive patients who were ineffective after 2 courses of standard regimens; patients relapsed within 12 months who underwent consolidation and intensive therapy after cr; patients relapsed after 12 months but were ineffective after conventional chemotherapy; patients with two or more relapses; patients with persistent extramedullary leukemia; patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-hsct) c. 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. 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) ≥ 50%; 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. active central nervous system leukemia; 2. known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide; 3. systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids); 4. 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. 5. history of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; 6. patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment; 7. women who are pregnant (urine/blood pregnancy test positive) or lactating; 8. suffering from a serious autoimmune disease or immunodeficiency disease; 9 suffering from mental illness; 10. known alcohol dependence or drug dependence; 11. according to the investigator's judgment, the patient has other unsuitable grouping conditions. -

Keywords: acute myeloid leukemia car-nk