Refractory systemic lupus erythematosus
Conditions
Interventions
The first dose group is 0.5×106 CAR-T/kg, with a dose error of ±20% allowed.:CAR-T cell injection solution
Dose expansion 1:CAR-T cell injection solution
The third dose group is 2.0×106 CAR-T/kg, with a dose error of ±20% allowed.:CAR-T cell injection solution
Dose expansion 2:CAR-T cell injection solution
The fourth dose group is 4.0×106 CAR-T/kg, with a dose error of ±20% allowed.:CAR-T cell injection solution
The second dose group is 1.0×106 CAR-T/kg, with a dose error of ±20% allowed.:CAR-T cell injection solution
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.All subjects or legal guardians must sign an informed consent form approved by the Ethics Committee before any screening procedure; 2.male and female; Be at least 18 years old and under 70 years old; Weight =100kg. 3.Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria, with a course of disease longer than 6 months. 4.At least 6 months of standard treatment prior to screening (defined as having received glucocorticoids and at least 2 immunosuppressants, such as cyclophosphamide, mycophenolic acid or its derivatives, azathioprine, methotrexate, cyclosporin, tachlimus, rituximab, Beliuzumab, tetacercep, etc., one of which must contain 1 biologic agent), Low disease activity status (LLDAS) has not been achieved for at least 3 months after use of each treatment (except for users who develop intolerance such as allergy, severe injection site reactions, hemototoxicy,liver and kidney function impairment, recurrent severe infections, etc.). Oral corticosteroids must meet the following requirements: 1) Prednisone (or equivalent) =7.5 mg/ day, and =60 mg/ day; 2) There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants and/or biologics; 5.SLEDAI-2000 score =7 during screening; 6.Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or anti-Smith antibodies; 7.C3 or/and C4 test results are lower than the lower limit of the laboratory reference value; 8.Life expectancy is greater than 6 months; 9.Fertile women (defined as all women biologically capable of becoming pregnant) who, at the time of informed consent, have a negative blood pregnancy test and must consent to the use of a highly effective contraceptive method for contraception for 2 years from the time of informed cell transfusion (including the period of dose-interrupted study therapy). Fertile men must agree to use an effective barrier method of contraception for 2 years from the time they become aware of cell transfusion, and should not donate semen or sperm throughout the study period.
Exclusion criteria
Exclusion criteria: 1.Subjects who have received any BCMA/CD19 cell therapy product or CAR-T therapy for any target prior to signing the informed consent; 2.Patients who underwent allogeneic blood transfusion, plasma exchange, hemodialysis, or intravenous immunoglobulin injection within 14 days before cell collection; 3.Patients with lupus crisis, or patients with other diseases requiring the use of drugs prohibited by the protocol, and the researchers judged that they were not suitable for inclusion; 4.Subjects with severely damaged vital organ functions: a. Renal function: the glomerular filtration rate (eGFR) estimated by the MDRD formula was 3 times the upper limit of normal, or total bilirubin >1.5 times ULN. c. Cardiovascular: Left ventricular ejection fraction (LVEF) 1.5×ULN. 5.Infectious diseases: active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, combined with hepatitis B virus DNA detection value =20IU/ml; Patients with chronic hepatitis B who meet the inclusion criteria should continue to receive preventive antiviral therapy according to the Chronic. 6.For patients with kidney involvement in SLE, renal biopsy results (ISN/RPS, 2003) within 1 year prior to screening showed complete type V (membranous lupus nephritis) or type VI (end-stage sclerosing lupus nephritis). 7.Patients with a history of > Grade 2 (CTCAE V5.0) bleeding within 30 days prior to screening, or long-term use of anticoagulants (such as warfarin coumarins or rivaroxaban new anticoagulants, except aspirin and clopidogrel); 8.Infectious diseases: Subjects with acute, life-threatening bacterial, viral or fungal infections that have not yet been controlled; 9.There are clinically significant central nervous system diseases or pathological changes related to SLE and non-SLE before screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, severe brain injury, dementia, Parkinson's disease, cerebellar disease, other organic brain syndromes or psychiatric diseases; 10.Subjects with previous or concurrent malignancies, but the following conditions can be enrolled: Basal cell or squamous cell carcinoma that has been adequately treated (adequate wound healing is required before the informed consent is signed); Carcinoma in situ of cervical or breast cancer that has been treated therapeutically and shows no signs of recurrence for at least 3 years prior to signing the informed consent; The primary malignancy has been completely resected and in complete remission for =5 years; 11.Live attenuated vaccine vaccination within 30 days p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of AE; | — |
Secondary
| Measure | Time frame |
|---|---|
| DORIS/LLDAS/SLEDAI-2000, etc; | — |
Countries
China
Contacts
Public ContactXie Qibing
West China Hospital of Sichuan University
Outcome results
None listed