Systemic Lupus Erythematosus
Conditions
Interventions
Moderate-dose group:FIT-(BCMA+CD19)-CAR-T cell injection
High-dose group:FIT-(BCMA+CD19)-CAR-T cell injection
Low-dose group:FIT-(BCMA+CD19)-CAR-T cell injection
Sponsors
The First Affiliated Hospital of Nanchang University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: To be eligible, patients had to meet all of the following criteria: 1. Voluntarily participate in the clinical research, I or legal guardian fully understand, informed the study and signed the informed consent form (ICF), willing to follow and complete all the trial procedures; 2. Age of 18-70 years old; 3. ECOG score =1.0×10^9/L; 2) hemoglobin >=60 g/L (in the absence of red blood cell transfusion within 14 days); 3) platelet count > 50×10^9/L (excluding thrombocytopenia due to autoimmune diseases as judged by the investigator); 4) absolute lymphocyte (ALC) >= 0.5×10^9/L; 5) serum total bilirubin 45%, absence of pericardial effusion confirmed by echocardiography (ECHO), and clinically insignificant results of electrocardiogram; 8. Baseline oxygen saturation >92% without supplemental oxygen; 9. Women of reproductive age must have a negative serum or urine pregnancy test report (women who have been surgically sterilized or who have been postmenopausal for at least 2 years are not considered fertile). 10. Male and female subjects who were willing to practice birth control from the time of signing the informed consent form until 12 months after completion of the last study drug administration. Relapsed/refractory systemic lupus erythematosus 1. Meets the 2019 European League against Rheumatism/American College of Rheumatology (EULAR /ACR) classification criteria for SLE; 2. Disease activity score SLEDAI-2000 =6 with at least one BILAG-2004 class A (severe manifestations) or two class B (moderate manifestations) organ scores, or both; Or disease activity score SLEDAI-2000 >=8 3. Relapsed/refractory was defined as disease activity after conventional therapy for more than 6 months or reoccurrence of disease activity after remission. Conventional treatment was defined as the use of glucocorticoids and cyclophosphamide, and any one or more of the following immunomodulatory drugs: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents including rituximab, belimumab, and taitacept. Recurrent/refractory Sjogren's syndrome 1. Meet the 2002 AECG criteria or 2016 ACR/ EULAR classification criteria for primary Sjogren's syndrome; (2) ESSDAI=6; 3. Positive anti-SSA /Ro antibody; 4. Relapsed/refractory was defined as disease activity after conventional therapy for more than 6 months or reoccurrence of disease activity after remission. Conventional treatment was defined as the use of glucocorticoids and cyclophosphamide, and any one or more of the following immunomodulatory drugs: antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents includin
Exclusion criteria
Exclusion criteria: Patients were excluded from the study if any of the following conditions were met: 1. Have active central nervous system disease, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system involvement; 2. Presence or suspected presence of fungal, bacterial (including but not limited to Mycobacterium tuberculosis), viral or other infections that are uncontrolled or require treatment with intravenous antibiotics; Simple urinary tract infections and uncomplicated bacterial pharyngitis were allowed. 3. Have hepatitis B (hepatitis B surface antigen positive and hepatitis B DNA>1000 copies /ml) or hepatitis C (hepatitis C antibody positive); Syphilis infection (antibody positive); Human immunodeficiency virus (HIV) infection; 4. Previous medications: 1) prior use of any CAR-T cell product or other gene-modified T cell therapy; 2) history of CD19-targeted therapy; 3) live vaccination within 4 weeks before enrollment; 4) use of other investigational medicinal products within 30 days before screening; 5) use of biomacromolecular drugs (e.g., rituximab, belimumab, telitercept, adalimumab, etanercept, etc.) with therapeutic effects in the target indication within 4 weeks or 5 half-lives before enrollment; 6) receiving >20mg/ day of prednisone or equivalent dose of another corticosteroid within 2 weeks before enrollment; 7) use of conventional synthetic drugs (e.g., cyclophosphamide, methotrexate, leflunomide, sulazalazine, etc.) for the target indication within 2 weeks before enrollment; 5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months before enrollment; 6. History of genetic syndromes with bone marrow failure, such as Fanconi anemia, Kosterman syndrome, Swachman-Diamond syndrome, etc. 7. History of lymphoproliferative diseases or malignancies (except basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix and other diseases in a disease-free state with no treatment in the past five years); 8. Women of reproductive age who are pregnant or breastfeeding; 9. Any medical activity that may interfere with the assessment of the safety or efficacy of the study; 10. It is unlikely, in the investigator's judgment, that the subject will complete all protocol-required study visits or procedures, including follow-up visits or compliance with requirements for study participation; Exclusion Criteria (Step 2) If the subject has any of the following conditions, the infusion should not be given or the infusion should be delayed. 1. Systemic fungal, bacterial, viral, or other infection is not controlled (defined as the presence of persistent symptoms/signs associated with the infection and no improvement despite appropriate antibiotic or other treatment). 2. Use of >10mg/ day of prednisone or equivalent doses of other corticosteroids within 72 hours before infusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type,frequency and severity of adverse events and laborary abnormalities;Percentage of subjects for whom the desired dose of FIT-(BCMA+CD19)-CAR-T cells can be successfully manufactured;The incidence of Dose-LimitingToxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum cytokine concentrations;Disease response rate;lncidence of CRS and ICANS;Immunogenicity of FIT-(BCMA+CD19)-CAR-T cells;Cellular kinetics of FIT-(BCMA+CD19)-CAR-T cells; | — |
Countries
China
Contacts
Public ContactFei Li; Rui Wu
The First Affiliated Hospital of Nanchang University
Outcome results
None listed