NCT07523555

Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies

A Phase 1/2, Open-Label, Nonrandomized, Multi-arm Umbrella Study of Biomarker-Selected Dual-Target CAR-T Cell Modules in Adults With Relapsed or Refractory Hematologic Malignancies

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Rationale. Relapse after single-target CAR-T therapy is often driven by antigen down-regulation, lineage plasticity, or pre-existing subclonal heterogeneity. A dual-target framework attempts to preserve depth of response while lowering the probability of escape through loss of one surface antigen. This example therefore uses a master protocol with disease-specific target modules rather than a one-size-fits-all construct. Screening and target selection. All participants undergo central immunophenotyping on bone marrow, peripheral blood, and/or involved tissue within 21 days before enrollment. A module is considered eligible when both antigens are detected on malignant cells by validated flow cytometry or equivalent assay and the anticipated on-target/off-tumor risk is acceptable. If more than one module qualifies, the target selection committee ranks options by disease-specific biology, antigen density, prior antigen-directed therapy, predicted escape risk, and manufacturability. Treatment schema. Participants undergo leukapheresis, optional bridging therapy, fludarabine/cyclophosphamide lymphodepletion, and infusion of the selected dual-target CAR-T module on Day 0. Depending on the module, the dual-target strategy may be delivered as a tandem/bicistronic product, compound product, or predefined sequential paired infusion if that is safer or more manufacturable for that antigen pair. Participants are monitored intensively through Day 28, followed for efficacy through Month 24, and may enter long-term gene-modified cell safety follow-up for up to 15 years if required by the final regulatory strategy.

Conditions

• Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
• Relapsed/Refractory B-cell Non-Hodgkin Lymphoma or CLL/SLL
• Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia
• Relapsed/Refractory Acute Myeloid Leukemia, High-risk Myelodysplastic Neoplasm
• BPDCN; Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia
• T-lymphoblastic Lymphoma
• Peripheral T-cell Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Autologous CD19/CD22 dual-target CAR-T module	Biological: Autologous CD19/CD22 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
BIOLOGICAL	Autologous CD19/CD20 dual-target CAR-T module	Biological: Autologous CD19/CD20 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
BIOLOGICAL	Autologous BCMA/CD19 dual-target CAR-T module	Biological: Autologous BCMA/CD19 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
BIOLOGICAL	Autologous BCMA/CD38 dual-target CAR-T module	Biological: Autologous BCMA/CD38 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
BIOLOGICAL	Autologous BCMA/GPRC5D dual-target CAR-T	Biological: Autologous BCMA/GPRC5D dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide
BIOLOGICAL	Autologous CD33/CD123 dual-target CAR-T module	Biological: Autologous CD33/CD123 dual-target CAR-T module (simultaneous or planned sequential paired infusion, module-specific) after lymphodepletion.
BIOLOGICAL	Autologous CD33/CLL1 dual-target CAR-T module	Biological: Autologous CD33/CLL1 dual-target CAR-T module after lymphodepletion with fludarabine/cyclophosphamide.
BIOLOGICAL	Autologous CD5/CD7 dual-target CAR-T module	Biological: Autologous CD5/CD7 dual-target CAR-T module (including sequential paired infusion if needed for manufacturing/safety) after lymphodepletion.

Timeline

• Start date: 2026-03-02
• Primary completion: 2027-03-14
• Completion: 2028-02-17
• First posted: 2026-04-13
• Last updated: 2026-04-13

Locations

1 site across 1 country: China