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

Korábbi kezelés

• Prior to screening, other lupus crises, such as active central nervous system lupus, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis.
• Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

Más betegség

• History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
• Other conditions that the investigator considered should not be enrolled in this clinical study.

Laborértékek

• IgA deficiency was present during screening (serum IgA level < 10 mg/dL).

• 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.
• SLEDAI-2000 score ≥8 during the screening period. Score ≥6 for SLEDAI-2000 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 ≥ 0.5×10\^9/L;
  • Platelet count ≥ 25×10\^9/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.
  • 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%.