CD19/BCMA HLA-independent TCR-T Cell Therapy for Refractory/Moderate-to-severe Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title: Clinical Study of the Safety and Efficacy of CD19/BCMA HLA-independent TCR-T Cell Therapy for Refractory/Moderate-to-severe Systemic Lupus Erythematosus

Status Not yet recruiting

Clinical Trial Summary

The purpose of the study is to explore the safety and efficacy of cluster of differentiation 19 (CD19)/B cell maturation antigen (BCMA) human leukocyte antigen (HLA)-independent T cell receptor (TCR) -T therapy in refractory/moderate-to-severe systemic lupus erythematosus(SLE).

Clinical Trial Description

The prognosis of patients with refractory/moderate-to-severe systemic lupus erythematosus (SLE) remains poor, due to two major therapeutic obstacles: (1) current treatment strategies including glucocorticoids, immunosuppressive agents, biological agents, are still difficult to achieve disease control, making the disease condition of some patients continue to be active or even worse; (2) some patients are unable to wean themselves off glucocorticoid and face the risk of numerous adverse effects caused by long-term glucocorticoid dependence, such as glucocorticoid-related diabetes, femoral head necrosis, hypertension, stress ulcers, and infection, etc. Therefore, there is a strong unmet clinical need for more effective treatment for patients suffering from refractory/moderate-to-severe SLE. Several preclinical and clinical studies have shown the efficacy of chimeric antigen receptor T (CAR-T) cell therapy in SLE. Compared with traditional CAR-T cell therapy, human leukocyte antigen (HLA)-independent T cell receptor (TCR) cell therapy can induce a controllable immune response and maintain a better response durability due to the mechanism of activation and regulation of the natural T cell antigen receptor, while releasing a lower level of cytokines, which can effectively minimizes toxicities. The aim of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of cluster of differentiation 19 (CD19)/B cell maturation antigen (BCMA) HLA-independent TCR-T cell therapy in refractory/moderate-to-severe SLE. Patients with refractory/moderate-to-severe SLE will be invited to participate in the study, to receive CD19/BCMA HLA-independent TCR-T cell intravenous infusion and follow-up visits of up to 1 years after enrollment. Given that the pretreatment chemotherapy (fludarabine,cyclophosphamide) of CAR-T therapy in current SLE clinical studies is mostly based on experiences in hematologic malignancies, which may cause severe complications such as infection, there is a lack of evidence-based rationale for patients with SLE to receive pretreatment chemotherapy. This study will explore the feasibility of TCR-T cell therapy without pretreatment chemotherapy in the treatment of refractory/moderate-to-severe systemic lupus erythematosus. ;

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

• NCT number: NCT06349343
• Study type: Interventional
• Source: Wuhan Union Hospital, China
• Contact: Qiubai Li, Professor
• Phone: 85726808
• Email: qiubaili@hust.edu.cn
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 2024
• Completion date: January 2026