NCT06996132

Bispecific Antibody-Based Salvage Therapy Followed by CAR-T ± ASCT in R/R Aggressive B-Cell Lymphoma

A Phase 2 Clinical Study of CD20×CD3 Bispecific Antibody-Based Salvage Therapy Followed by CAR-T With or Without ASCT in R/R Aggressive B-Cell Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study consists of two sequential treatment phases. In the first phase, patients with r/r aggressive B-NHL receive two cycles of glofitamab ± investigator-selected agents. In the second phase, patients eligible for CAR-T monotherapy undergo FC lymphodepletion followed by CAR-T infusion (2-4×10⁶/kg), while those eligible for CAR-T+ASCT receive conditioning chemotherapy with PBSC reinfusion on day 0 and CAR-T administration (2-4×10⁶/kg) on day +3 (±1). Patients demonstrating Deauville 4-5 or ctDNA positivity at day 28 post-CAR-T infusion subsequently receive four cycles of glofitamab consolidation therapy.

Detailed description

The study comprises two sequential treatment phases. In the first phase, eligible patients with r/r aggressive B-NHL receive 2 cycles of glofitamab ± X regimen (where X includes but is not limited to chemotherapy, antibody-drug conjugates, or small-molecule targeted agents, selected at the investigator's discretion). Peripheral blood lymphocyte apheresis is performed prior to initial glofitamab administration unless clinically contraindicated, with hematopoietic stem cell mobilization and collection timed per investigator assessment to achieve minimum required yields of ≥3×10⁸/kg mononuclear cells and ≥2×10⁶/kg CD34+ cells. Patients successfully completing phase 1 proceed to phase 2 treatment. In the CAR-T alone cohort, patients receive FC lymphodepleting therapy (days -5 to -3) followed by CAR-T cell infusion (2-4×10⁶/kg) on day 0. The CAR-T+ASCT cohort undergoes conditioning chemotherapy (regimen determined by investigator) with autologous PBSC reinfusion on day 0 and CAR-T cells (2-4×10⁶/kg) administered on day +3 (±1 day). At day 28 post-CAR-T infusion, patients demonstrating PET-CT Deauville scores of 4-5 or ctDNA positivity initiate 4 cycles of glofitamab consolidation therapy.

Conditions

• Relapsed or Refractory Aggressive B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	Glofitamab	Glofitamab is administered as monotherapy or in combination with investigator-selected agents (including but not limited to chemotherapy, ADCs, BTK inhibitors, etc.) for 2 cycles.
DRUG	Chimeric Antigen Receptor T Cells (CAR-T)	After two cycles of glofitamab-based salvage therapy, single-target or dual-target CAR-T cells directed against CD19, CD20, and/or CD22 are infused following lymphodepleting (fludarabine + cyclophosphamide) or myeloablative conditioning, at a dose of 2-4 × 10⁶/kg.

Timeline

• Start date: 2025-05-09
• Primary completion: 2027-05-30
• Completion: 2027-12-30
• First posted: 2025-05-30
• Last updated: 2025-06-17

Locations

1 site across 1 country: China