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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory
• Intervention / Treatment: Drug: JD123 injection

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Principal Investigator: Xiao-jun Huang, MD
      • Contact: Meng Lv, MD PhD; Phone Number: +861088324637; Email: drlvmeng@bjmu.edu.cn
      • Sub-Investigator: Xiang-yu Zhao, MD PhD
      • Sub-Investigator: Meng Lv, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Experimental: JD123 injection.; 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-month DLTs	Dose limiting toxicities (DLTs)	1-month

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Beijing JD Biotech Co. LTD.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: December 30, 2023
• First Submitted That Met QC Criteria: December 30, 2023
• First Posted (Estimated): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: December 30, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; CAR-NK
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2023PHD016-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No