NCT06125652

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

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Xuzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	anti Tim-3/CD123 CAR-T cell therapy	Enrolled patients will receive prespecified dose of autologous CAR-T cells.

Timeline

• Start date: 2023-11-04
• Primary completion: 2026-01-01
• Completion: 2027-01-01
• First posted: 2023-11-09
• Last updated: 2023-11-09

Locations

1 site across 1 country: China