Off-the-shelf CD123 CAR-NK for R/R AML

Peking University

Status and phase: Enrolling; Early Phase 1

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

Treatments: Drug: JD123 injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06201247

2023PHD016-001

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 12 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

9. Known alcohol dependence or drug dependence; 11. According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Experimental: Experimental: JD123 injection.

Experimental group

Description:

The relapsed/refractory AML patients will receive JD123 injections up to 3 dose levels (5.0×108 cells/dose，1.5×109 cells/dose，3.0×109 cells/dose) after FC chemotherapy.

Treatment:

Drug: JD123 injection