This is a single-center, open-label, non-randomized, single-arm clinical trial. Patients with refractory lupus neritis (SLE-LN), systemic sclerosis (SSc), primary Sjogren syndrome combined with pulmonary artery hypertension (pSS-PAH) and other autoimmune diseases (AID) receive CD19-BCMA CAR T cell therapy. Phase I (Dose-Escalation/Dose-De-escalation Phase)：The primary objective is to prospectively assess the safety of CD19-BCMA CAR T cell therapy in patients with SLE-LN, SSc, pSS-PAH and other autoimmune diseases (AID).Phase I (Dose-Escalation/Dose-De-escalation Phase)：Primary Endpoint: Safety, tolerability, and determination of the optimal biological dose (OBD) and the Phase II recommended dose (RP2D) in patients with SLE-LN, SSc, pSS-PAH, and other autoimmune diseases (AID).Phase II (Dose-Expansion Phase):Overall remission rate (ORR) \[Time Frame: 90,180 Days\]
Refractory Lupus Nephritis（LN）: Patients who meet all the following requirements can be enrolled in the group.
Male or female, aged 10-65 years;
Meeting the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for Systemic Lupus Erythematosus (Appendix 4);
The ANA result is positive which means ANA titer≥ 1:80 (based on the equivalent detection results by Hep-2 immunofluorescence assay or enzyme immune assay), and/or according to the detection results from center laboratory, during the screening visit,the anti dsDNA serum antibody test is positive (based on ELISA assay, ≥30 IU/mL);
Intracranial hypertension or disorder of consciousness;
Symptomatic heart failure or severe arrhythmia;
Symptoms of severe respiratory failure;
Complicated with other types of malignant tumors;
Single group
CD19-BCMA CAR-T cells infusion
DrugApproximately 3-5 days prior to CD19-BCMA CAR-T cell infusion, subjects are treated with FC regimen (fludarabine and cyclophosphamide) for lymphodepletion. CAR-T cell infusion are performed 48 h after completion of chemotherapy.
Phase I (Dose-Escalation/Dose-De-escalation Phase)
Dose-limiting toxicity (DLT) \[Time Frame: 28 days\] Incidence and type of dose-limiting toxicity(DLT) within 28 days of CD19-BCMA CAR-T infusion. Adverse events (AEs) \[Time Frame: 30 days\] Total number, incidence and severity of adverse events (AEs) within 30 days of CD19-BCMA CAR-T infusion
Phase II (Dose-Expansion Phase)
Overall remission rate (ORR)
Phase I (Dose-Escalation/Dose-De-escalation Phase)
Overall remission rate (ORR) \[Time Frame: 90,180 Days\]: The assessment of ORR by dose group at 90 and 180 days after CD19-BCMA CAR-T infusion (per disease-specific criteria: SLE-LN SRI-4/LLDAS/DORIS; SSc EUSTAR AI; pSS-PAH ESSDAI + PAH response per ESC/ERS 2022). CAR T-Cell Pharmacokinetics \[Time Frame: Up to 2 Years\] Incidence and Grading of SAEs From 30 Days to 2 Years Post-CD19-BCMA CAR-T Infusion
Phase II (Dose-Expansion Phase)
Incidence and Grading of AEs； CAR T-Cell Pharmacokinetics； Overall survival (OS), duration of response (DOR)
Click on the lead sponsor to view all of their trials.
