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

Acute Myeloid Leukemia, in Relapse Clinical Trial

Official title:

Safety and 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06201247
• Other study ID #: 2023PHD016-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 30, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2023
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Acute Myeloid Leukemia, in Relapse
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• JD123 injection
JD123 injection is an universal Off-the-shelf CD123-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) therapy derived from a healthy donor.

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing JD Biotech Co. LTD.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-month DLTs	Dose limiting toxicities (DLTs)	1-month
Secondary	3-month CR/CRi	Complete response (CR) or Complete remission with incomplete recovery(CRi)	3-month
Secondary	1-year PFS	Progression free survival(PFS)	1-year
Secondary	1-year OS	Overall Survival (OS)	1-year
Secondary	1-year MRD(-)	Proportion of subjects with minimal-residual disease (MRD) negative response	1-year
Secondary	3-month AUC	The area under the concentration time-curve (AUC) of CD123-CAR-NK cells	3-month
Secondary	3-month Peak	Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax)	3-month