Exploratory Clinical Study of CNCT19 Anti CD19 Cell Therapy in the Treatment of Refractory Autoimmune Diseases

Inclusion Criteria22

• The enrolled subjects or their legal representatives signed informed consent form;
• age range: 18-70 years (including 18 and 70 years), male or female;
• Subjects with refractory systemic lupus erythematosus (lupus nephritis, immune thrombocytopenia) : Diagnosed with systemic lupus erythematosus according to American College of Rheumatology (ACR) criteria, accompanied by lupus nephritis (SLE-LN) or immune thrombocytopenia (SLE-ITP) and receiving standard treatment;
• Subjects with Refractory Systemic Lupus Erythematosus (Lupus Nephritis): Active and biopsy-confirmed proliferative lupus nephritis grade III or IV or simple grade V alone according to 2003 ISN/RPS criteria. Active renal disease was defined as a urine protein: creatinine ratio > 1.0 or proteinuria > 3.5 grams/day.
• Subjects with refractory systemic lupus erythematosus (thrombocytopenia): At least two consecutive blood routine examinations showed that platelet was lower than 50x109/L; Blood cell morphology of peripheral blood smear was normal. The spleen is generally not enlarged; The morphological characteristics of bone marrow cells were megakaryocytic increase or normal, accompanied by maturation disorder. Platelet count > 10 x10\^9 / L.
• Subjects with refractory ANCA-associated vasculitis: diagnosis of ANCA glomerulonephritis (GN) or vasculitis based on the 2013 American Chapel Hill Consensus Conference definition of AAV ;
• Relapsed or refractory AAV requiring treatment with cyclophosphamide or rituximab
• Newly diagnosed or recurrent AAV--, defined as accumulation of at least one major organ (e.g., kidney, lung, heart) requiring induction therapy with cyclophosphamide or rituximab;
• Anti-PR3 or anti-MPO positive (current or history);
• Subjects with Refractory Dermatomyositis: Refractory MDA5-positive dermatomyositis is defined as active disease and meets the following conditions: adequate corticosteroid therapy (greater than two to four weeks of conventional corticosteroid therapy or intolerance to such therapy) and/or
• Use of ≥ 1 conventional immunosuppressive agent (eg, methotrexate, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF, or rituximab) at a reasonable dose and duration (greater than two to four weeks or intolerance to therapy);
• Treatment with IVIG or cyclophosphamide for two to four weeks.
• Women of childbearing potential must have a negative blood pregnancy test 7 days prior to trial conditioning therapy; any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 1 year following reinfusion of CNCT19 CAR-T cells. Childbearing potential, in the judgment of the investigator, is biologically capable of bearing a living baby and sexually active. Female patients who were not of childbearing potential (ie, met at least 1 of the following criteria):
• Hysterectomy or oophorectomy, or
• Medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence of pathological or physiological causes).
• Adequate organ function according to the following criteria:
• Aspartate aminotransferase (AST) ≤ 3 times of upper limit of normal (ULN);
• Alanine aminotransferase (ALT) ≤ 3 times ULN;
• Total serum bilirubin ≤ 2 times ULN unless the patient has documented Gilbert's syndrome; patients with Gilbert's syndrome who have bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included;
• Serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula), Patients with lupus nephritis may relax the conditions appropriately according to the judgment of the investigator;
• Must have minimal pulmonary reserve and oxygen saturation > 91% in a nonoxygenated state;
• Lymphocyte count > 0.4 × 109/L.