Administration of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)

NCT ID: NCT06125652

Last Updated: 2023-11-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-04
• Study Completion Date: 2027-01-01

Brief Summary

To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of relapsed and refractory acute myeloid leukemia.

Detailed Description

Cluster of Differentiation 123 (CD123) is usually overexpressed on leukemia stem cells (LSCs) in acute myeloid leukemia (AML). However, CD123 has poor specificity and is also expressed on normal hematopoietic stem cells (HSC), myeloid cells, and some non-hematopoietic cells. This leads to widespread on-target off-tumor effect in the clinical application of anti CD123 CAR-T cells, manifested as severe bone marrow suppression, organ damage, and patients experiencing infections, bleeding, and organ dysfunction. T cell immunoglobulin and mucin domain 3 (Tim-3) belongs to the Tim gene family. 85% of LSCs highly express Tim-3, while normal hematopoietic stem/progenitor cells (HSC/P), granulocytes, and macrophages do not express Tim-3. Compared with CD123, seeing Tim-3 as a recognition tool for LSCs has higher specificity. In vivo and in vitro studies have confirmed that anti Tim-3 CAR-T cells have significant anti LSCs effects, while not affecting the ability of normal HSC/P to form colonies and differentiate lineages. We believe that using both Tim-3 and CD123 as targets for CAR-T cells can improve the specificity of recognizing LSCs, reduce the killing effect of CAR-T cells on HSC/P expressing CD123, and thus reduce the on-target off-tumor effect.

Conditions

Acute Myeloid Leukemia Refractory; Acute Myeloid Leukemia, in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anti Tim-3/CD123 CAR-T cell therapy

Enrolled patients will receive prespecified dose of autologous CAR-T cells.

Group Type: EXPERIMENTAL

anti Tim-3/CD123 CAR-T cell therapy

Intervention Type: DRUG

Enrolled patients will receive prespecified dose of autologous CAR-T cells.

Interventions

anti Tim-3/CD123 CAR-T cell therapy

Enrolled patients will receive prespecified dose of autologous CAR-T cells.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;

2. At the age of 18-70 years old;

3. Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);

4. The patient has recovered from the toxicity of previous treatment;

5. ECOG score ≤ 2 and expected survival period is not less than 3 months;

6. Adequate organ function defined as:AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%;

7. Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test;

8. From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception.

Exclusion Criteria

1. Diagnosis of acute promyelocytic leukemia;

2. History or presence of a CNS disorder;

3. HBsAg is positive; HCV #HIV or Syphilis antibody are positive, CMV-DNA in peripheral blood is more than≥500 copies /mL;

4. History of severe hypersensitivity reaction;

5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;

6. History of organ transplant surgery;

7. Required systemic application of immunosuppressive or other drugs;

8. Auto-SCT within the 3 months before enrollment;

9. Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES));

10. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ;

11. Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management;

12. Live vaccine received within the ≤ 4 weeks before enrollment;

13. Persons with serious mental illness;

14. History of major surgical operations four weeks before enrollment;

15. History of alcoholism or substance abuse;

16. Was identified by the investigators as unsuitable to participate in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Kai Lin Xu，MD

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kailin Xu, MD.,PD.

Role: STUDY_CHAIR

The Affiliated Hospital oh Xuzhou Medical University

Locations

Kailin Xu

Xuzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Kailin Xu, MD.,PD.

Role: CONTACT

lihmd@163.com

15162166166

Facility Contacts

Kailin Xu, M.D., Ph.D.

Role: primary

lihmd@163.com

15162166166

Other Identifiers

XYFY2023-KL358-01

Identifier Type: -

Identifier Source: org_study_id