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CLL-1/CD70 Dual-Target CAR-T Cell Therapy for Acute Myeloid Leukemia
Sponsor: Liping Dou
Summary
This is a single-center, open-label, single-arm, prospective, investigator-initiated dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of an autologous CLL-1/CD70 dual-target CAR-T cell injection in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML; acute promyelocytic leukemia excluded). After leukapheresis for CAR-T cell manufacture, participants receive lymphodepleting conditioning (fludarabine 30 mg/m\^2/day plus cyclophosphamide 300 mg/m\^2/day on Days -5 to -3), followed by a single intravenous infusion of CLL-1-CD70 CAR-T cells. Dose escalation follows a traditional 3+3 design with planned dose levels of 0.5 x 10\^6, 1 x 10\^6, and 2 x 10\^6 CAR-T cells/kg, guided by dose-limiting toxicities (DLTs) assessed during Days 1-28 after infusion. The primary endpoint is safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, infections, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and tumor lysis syndrome (TLS). Efficacy will be evaluated by the composite complete remission rate (CRc, defined as the proportion of patients achieving CR, CRh, or CRi) at prespecified time points according to the European LeukemiaNet (ELN) 2022 criteria, overall survival (OS), event-free survival (EFS), duration of response (DOR), and cumulative incidence of relapse (CIR) over a 1-year follow-up period. Immune reconstitution following CAR-T cell infusion will also be assessed at prespecified time points. CAR-T cellular kinetics in peripheral blood (CAR transgene copies, Cmax, Tmax, and AUC0-28d) will also be evaluated.
Official title: A Clinical Study on the Safety of Bispecific CLL-1-CD70 Dual-Target CAR-T Therapy for Acute Myeloid Leukemia
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
12
Start Date
2026-11-30
Completion Date
2029-11-30
Last Updated
2026-10-27
Healthy Volunteers
No
Interventions
CLL-1-CD70 CAR-T Cell Injection
CLL-1-CD70 CAR-T Cell Injection is an investigational autologous dual-target CAR T-cell therapy (lentiviral vector-based) directed against CLL-1 and CD70, for patients with relapsed or refractory (R/R) acute myeloid leukemia (acute promyelocytic leukemia excluded). After leukapheresis and lymphodepleting conditioning (fludarabine plus cyclophosphamide), participants receive a single intravenous infusion at protocol-specified dose levels (0.5 x 10\^6, 1 x 10\^6, or 2 x 10\^6 CAR-T cells/kg). Dose escalation follows a traditional 3+3 design and is guided by the occurrence of dose-limiting toxicities (DLTs).
Locations (1)
Chinese PLA General Hospital
Beijing, Beijing Municipality, China