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

Acute Myeloid Leukemia Refractory Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05574608
• Other study ID #: CAR-NK123-JD
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 1, 2022
• Est. completion date: October 30, 2024

Study information

• Verified date: April 2023
• Source: Affiliated Hospital to Academy of Military Medical Sciences
• Contact: Liangding Hu, Doctor
• Phone: +86 01066947171
• Email: huliangding[@]sohu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 of CD123-CAR NK cells given to these patients.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: October 30, 2024
• Est. primary completion date: October 30, 2023
• 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 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Recurrent
• Acute Myeloid Leukemia Refractory
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
China	The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Affiliated Hospital to Academy of Military Medical Sciences	Beijing JD Biotech Co. LTD.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLTs)		1 Months
Primary	Treatment-emergent adverse events		3 months
Primary	Treatment-related adverse events		3 months
Secondary	Complete response (CR)		3 months
Secondary	Progression free survival (PFS)		12 months
Secondary	Overall Survival (OS)		12 months
Secondary	Proportion of subjects with minimal-residual disease (MRD) negative response		3 months
Secondary	The area under the concentration time-curve (AUC) of CD123-CAR-NK cells		3 Months
Secondary	Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax)		3 Months