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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia Refractory; Acute Myeloid Leukemia Recurrent
• Intervention / Treatment: Biological: CD123-CAR-NK cells

Detailed Description

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.

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

Contacts and Locations

• Study Contact: Name: Liangding Hu, Doctor; Phone Number: +86 01066947171; Email: huliangding@sohu.com
• Study Contact Backup: Name: Yao Sun, Doctor; Phone Number: +86 01066947172; Email: suny320@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital
      • Contact: Liangding Hu, Ph.D; Phone Number: +86-010-6694-7171; Email: huliangding@sohu.com
      • Contact: Yao Sun, Ph.D; Phone Number: +86-010-6694-7172; Email: suny320@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (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 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

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. Central nervous system involved;
2. Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide;
3. Systemic use of hormones within 2 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Experimental: CD123-CAR-NK.; 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; CD123-CAR-NK is an allogenic CD123-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences
• Collaborators: Beijing JD Biotech Co. LTD.
• Investigators: Principal Investigator: Liangding Hu, Docotr, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): October 30, 2023
• Study Completion (Anticipated): October 30, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CAR-NK123-JD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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