Allogenic CD123-CAR-NK Cells in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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The CD123-Targeted CAR-NK cell therapy is a new treatment that is being investigated for treatment of acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety of CD123-CAR NK cells given to these patients.

Detailed Description
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This is a study of allogenic CD123-CAR NK cells. The relapsed/refractory AML patients will receive FC (F, Fludarabine, C, Cyclophosphamide) chemotherapy followed by infusion of CD123-CAR-NK cells. 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.

Official Title
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Early Clinical Study of Allogenic CD123-CAR-NK Cells (JD023 Injection) in the Treatment of Refractory or Relapsed CD123-positive Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia Recurrent

Intervention / Treatment
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* Biological: CD123-CAR-NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 18 years old, no gender or race; Expected survival period ≥ 3 months; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; The diagnosis of AML with bone marrow biopsy, immunohistochemistry or Flow cytometry definitively positive for CD123 and met one of 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; C. Patients eligible for relapsed or refractory AML remained minimally residual disease positive after salvage therapy 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%; 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; Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide; Systemic use of hormones within 2 weeks prior to enrollment (except for patients with inhaled corticosteroids); 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Evaluate the safety of JD023 injection.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Experimental: CD123-CAR-NK.<br>The relapsed/refractory AML patients will receive allogenic CD123-Targeted CAR-NK cells infusion (1x10^9, 1-2x10^7/kg) after precondition chemotherapy. | Biological: CD123-CAR-NK cells<br>* CD123-CAR-NK is an allogenic CD123-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) |  | 1 Months | 
| Treatment-emergent adverse events |  | 3 months | 
| Treatment-related adverse events |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) |  | 3 months | 
| Progression free survival (PFS) |  | 12 months | 
| Overall Survival (OS) |  | 12 months | 
| Proportion of subjects with minimal-residual disease (MRD) negative response |  | 3 months | 
| The area under the concentration time-curve (AUC) of CD123-CAR-NK cells |  | 3 Months | 
| Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax) |  | 3 Months |