Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Moderate to Severe Active SLE Clinical Research

Inclusion Criteria30

• All subjects or guardians must sign an informed consent form approved by the Ethics Committee in person before commencing any screening process;
• Be over 18 years of age, male or female;
• A diagnosis of SLE according to the 2012 systemic lupus international collaborating clinics(SLICC);
• The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening:
• Conventional regimens for SLE are corticosteroids and one or more immunomodulatory drugs over 6 months；
• Oral corticosteroids must meet the following requirements:
• Prednisone (or equivalent) ≥7.5 mg/ day, and ≤60 mg/ day；
• There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants；
• At least 8 weeks of treatment prior to screening, and the dose must be kept stable for > 2 weeks.
• Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or anti-Smith antibodies；
• SELENA-SLEDAI score ≥8 during the screening period. Score ≥6 for SELENA-SLEDAI clinical symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or anti-DS-DNA antibody score is present；
• Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo;
• CD19 expression was positive by or flow cytometry ;
• Organ function：
• Complete blood count (CBC) test \[the following criteria should be met within 24 hours prior to apheresis, and supportive treatment such as transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) should be avoided within 7 days prior to detection\]
• Lymphocyte count ≥ 0.5×109/L (except for those receiving bridging chemotherapy);
• Platelet count ≥ 25×109/L;
• Hemoglobin ≥ 70.0 g/L
• Blood Biochemistry:
• Serum creatinine (Scr) ≤ 1.5 x ULN, or
• endogenous creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault formula);
• alanine aminotransferase (ALT) ≤ 2.5 x ULN;
• aspartate aminotransferase (AST) ≤ 2.5 ×ULN;
• Total bilirubin (TBIL) ≤ 2 ×ULN; Subjects with total bilirubin < 3 × ULN and direct bilirubin < 1.5× ULN with Gilbert-.Meulengracht syndrome could be included;
• Serum lipase and amylase ≤ 1.5×ULN;
• Alkaline phosphatase (ALP) ≤ 2.5 ×ULN;
• In case of bone or liver metastasis, AST, ALT and ALP ≤ 5 ×ULN;
• Prothrombin time (PT) extended ≤ 4 s, fibrinogen ≥ 1 g/L, activated partial thromboplastin time (APTT) ≤ 1.5 ×ULN;
• Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) > 91% in indoor air environment..
• Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45％.