Clinical Research Studies

SLE disease activity results in accumulation of tissue and organ damage (eg, nephritis, multisystem organ failure, and central nervous disease) that contributes to morbidity and premature death. In addition to increased risk of mortality, SLE may have a profound effect on quality of life, with fatigue, pain, and disease flares contributing to disability. Despite extensive efforts to develop novel therapies for SLE, there remains an unmet need for novel therapies, particularly for treatment refractory patients and those who suffer from acute and long-term treatment-related toxicities, including recurrent infections, osteoporosis, accelerated cardiovascular disease, and infertility. Failure to respond and/or achieve a complete clinical response following treatment with systemic glucocorticoids and 2 or more immunosuppressive drugs indicates refractory disease with a poor overall prognosis and little expectation of achieving remission. New treatments for such severe, refractory cases are urgently needed. This study will enroll participants with SLE who have a severe, life-threatening disease course and have been refractory to currently available therapies. Because of the recognized pathogenic role of autoreactive B cells and plasmablasts in patients with SLE, the current study will explore the potential utility of depletion of CD19+ B cells and plasmablasts with CD19-specific CAR T cells in this dose-ranging study to achieve deep and sustained elimination of autoreactive B cells and plasmablasts, inducing disease remission and potentially restoring humoral immune tolerance. The present study aims to establish the tolerability and preliminary efficacy of the leukapheresis, lymphodepletion and infusion of the study intervention, CC-97540, as well as the pharmacokinetics of CC-97540, and depth and duration of B cell depletion.