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

Sponsor
Affiliated Hospital to Academy of Military Medical Sciences (Other)
Overall Status
Recruiting
CT.gov ID
NCT05574608
Collaborator
Beijing JD Biotech Co. LTD. (Other)
12
1
1
25
0.5

Study Details

Study Description

Brief Summary

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 and maximum tolerated dose of CD123-CAR NK cells given to these patients.

Condition or Disease Intervention/Treatment Phase
  • Biological: CD123-CAR-NK cells
Early Phase 1

Detailed Description

This is a dose-escalation 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 Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Evaluate the safety of JD023 injection, including dose-limiting toxicity (DLT) and adverse events (AE), etc.Evaluate the safety of JD023 injection, including dose-limiting toxicity (DLT) and adverse events (AE), etc.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Early Clinical Study of Allogenic CD123-CAR-NK Cells (JD023 Injection) in the Treatment of Refractory or Relapsed CD123-positive Acute Myeloid Leukemia
Actual Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Oct 30, 2023
Anticipated Study Completion Date :
Oct 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental: Experimental: CD123-CAR-NK.

The relapsed/refractory AML patients will receive allogenic CD123-Targeted CAR-NK cells infusion up to 3 dose levels (1x10^6/kg, 5x10^6/kg, 2x10^7/kg) after FC chemotherapy.

Biological: CD123-CAR-NK cells
CD123-CAR-NK is an allogenic CD123-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicities (DLTs) [1 Months]

  2. Treatment-emergent adverse events [3 months]

  3. Treatment-related adverse events [3 months]

Secondary Outcome Measures

  1. Complete response (CR) [3 months]

  2. Progression free survival (PFS) [12 months]

  3. Overall Survival (OS) [12 months]

  4. Proportion of subjects with minimal-residual disease (MRD) negative response [3 months]

  5. The area under the concentration time-curve (AUC) of CD123-CAR-NK cells [3 Months]

  6. Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax) [3 Months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:

  1. 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;
  1. Adequate organ function:
  1. 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%;
  1. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.;

  2. 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 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital Beijing Beijing China 100071

Sponsors and Collaborators

  • Affiliated Hospital to Academy of Military Medical Sciences
  • 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Affiliated Hospital to Academy of Military Medical Sciences
ClinicalTrials.gov Identifier:
NCT05574608
Other Study ID Numbers:
  • CAR-NK123-JD
First Posted:
Oct 10, 2022
Last Update Posted:
Oct 26, 2022
Last Verified:
Oct 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 26, 2022