CD19/BCMA UCAR-T for B Cell-Related Autoimmune Disease

1. Background and Rationale • This study investigates a novel cell therapy for patients with relapsed or refractory B-cell-mediated autoimmune diseases (AID). QT-219CX Cell Injection is a universal allogeneic CAR-T cell product derived from healthy donors, designed to target both CD19 and BCMA. Dual-Targeting Design: By targeting both CD19+ B cells and BCMA+ plasma cells, the therapy aims to achieve deep and extensive depletion of pathogenic immune cells, potentially leading to immune "resetting". 2. Study Objectives * Primary Objective: To evaluate the safety, tolerability, and preliminary efficacy of QT-219CX in subjects with B-cell-related autoimmune diseases, and to determine the Dose-Limiting Toxicities (DLTs). * Secondary Objective: To characterize the pharmacokinetics (PK, e.g., transgene copy numbers) and pharmacodynamics (PD, e.g., cytokine levels and B-cell depletion) of QT-219CX. * Exploratory Objective: To explore correlations between baseline status (e.g., NK cell phenotype), PK/PD, safety, and efficacy, as well as the impact on growth and development (Tanner stage) in pediatric subjects. 3. Study Design and Dose Escalation ：This is an open-label, single-arm, dose-escalation, and expansion study. Dose Escalation: A standard "3+3" design is employed, with an estimated 6-15 subjects in this phase. * Enrollment Priority: Enrollment will prioritize older pediatric subjects. 4. Clinical Procedures • Screening (Day -28 to -5): Subjects provide informed consent and undergo baseline laboratory and imaging assessments. • Conditioning : Subjects receive a lymphodepletion regimen. • Infusion (Day 0): Upon confirming adequate organ function and absence of active infection, a single intravenous dose of QT-219CX is administered. • DLT Observation (Day 0 to 28): Subjects are closely monitored for 28 days post-infusion to assess hematologic and non-hematologic toxicities. 5. Follow-up and Efficacy Evaluation • Safety Management: Intensive monitoring for Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), GvHD, infections, and viral reactivation . Efficacy Assessment: Evaluations are conducted at Days 28, 60, 90, and 180, with Day 90 and Day 180 serving as key clinical efficacy time points. • Long-term Follow-up: Starting six months post-infusion, subjects enter a long-term follow-up phase with visits every 3 months for up to 2 years or as clinically indicated.