NCT04662099

T Cells Expressing a Bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

Safety and Efficacy of the Bispecific CAR T Therapy Targeting CS1 and BCMA in Patients With Relapsed/ Refractory Multiple Myeloma: a Single-center, Open-label, Single-arm Clinical Study

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of the bispecific CAR T cells targeting CS1 and BCMA in patients with relapsed or refractory multiple myeloma.

Detailed description

* Multiple myeloma(MM) is one of the most common hematological malignancies with substantial morbidity and mortality. * In recent years, several new therapies have prolonged survival of patients with MM, but it is still an incurable malignancy of plasma cells. * B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and a small subset of B cells. This specific expression pattern makes BCMA an ideal target antigen for immunotherapies in MM. * BCMA-targeted chimeric antigen receptor (CAR) T cells have exhibited significant efficacy in MM, but relapse due to single-target escape or poor in vivo persistence has been reported. * Dual-targets or sequential infusion have been proposed to reduce relapse and improve outcomes post BCMA-specific CAR T therapies. * CS1 is expressed on pro-B cells and plasma cells especially malignant ones and some evidence suggests it plays a role in stromal cell interaction in the BM tumour microenvironment. * We have constructed a bispecific CAR containing anti-CS1 single chain variable region (scFv) and an anti-BCMA scFv in 4-1BB-containing second-generation formats. * The bispecific CAR T cells have exhibited potent cytotoxicity in various BCMA+ or/and CS1+ MM cells and can effectively eradicate MM cells in xenograft mice models. * This study aims to evaluate prelimary safety and efficacy of the CS1\&BCMA CAR T cells in patients with relapsed or refractory MM.

Conditions

• CS1+ or BCMA+ Multiple Myeloma

Interventions

Type	Name	Description
BIOLOGICAL	Conditioning chemotherapy followed by CAR T cell infusion	Conditioning chemotherapy: Cyclophosphamide 250 mg/m\^2 and fludarabine 30 mg/m\^2 IV infusion on days -5, -4, and -3 CAR T cells infusion: 0.75x10\^6-3.0X10\^6 CAR+ T cells per kg of recipient bodyweight. if DLTs don't occur at the dose of 3.0X10\^6 CAR+ T cells per kg, the investigators will discuss whether to try higher dose.

Timeline

• Start date: 2020-03-25
• Primary completion: 2023-12-30
• Completion: 2023-12-30
• First posted: 2020-12-10
• Last updated: 2023-08-16

Locations

1 site across 1 country: China