Study Summary
Phase 1/2 umbrella study evaluates biomarker-selected dual-target CAR-T cell modules for adults with relapsed or refractory hematologic malignancies. After central antigen co-expression screening, participants are assigned to the most appropriate active dual-target module: CD19/CD22, CD19/CD20, BCMA/CD19, BCMA/CD38, BCMA/GPRC5D, CD33/CD123, CD33/CLL1, or CD5/CD7. Phase 1 determines safety, dose-limiting toxicities, and the recommended phase 2 dose for each module; phase 2 estimates preliminary antitumor activity, including overall response rate and MRD-negative response.
Lymphodepletion with fludarabine/cyclophosphamide precedes infusion. The design is intended to reduce antigen escape by matching disease biology and target co-expression to a rational dual-target strategy.
Interventions
Autologous CD19/CD22 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous CD19/CD22 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Autologous CD19/CD20 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous CD19/CD20 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Autologous BCMA/CD19 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous BCMA/CD19 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Autologous BCMA/CD38 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous BCMA/CD38 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Autologous BCMA/GPRC5D dual-target CAR-TBIOLOGICAL
Biological: Autologous BCMA/GPRC5D dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide
Autologous CD33/CD123 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous CD33/CD123 dual-target CAR-T module (simultaneous or planned sequential paired infusion, module-specific) after lymphodepletion.
Autologous CD33/CLL1 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous CD33/CLL1 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
Autologous CD5/CD7 dual-target CAR-T moduleBIOLOGICAL
Biological: Autologous CD5/CD7 dual-target CAR-T module (including sequential paired infusion if needed for manufacturing/safety) after lymphodepletion.