Systemic Lupus Erythematosus (SLE)
Conditions
Interventions
Treatment group:Infusion of anti-CD19-CAR T cell injection
Sponsors
The First Affiliated Hospital of Wenzhou Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily participate in clinical research. The person or legal guardian fully understands and informs the research and signs the informed consent form (ICF), and is willing to follow and complete all trial procedures; 2.Aged 18-65 years old; 3.ECOG score = 2 points; 4.Expected survival period is at least 12 weeks; 5.Have good intravenous access (for apheresis) and have no other contraindications to blood cell separation; 6.When screening patients, laboratory tests must meet the following requirements and they must not have received cell growth factors within 7 days before screening hematology assessment (long-acting colony-stimulating factor (G-CSF/PEG-CSF) requires an interval of 2 weeks): 1) Absolute neutrophil count =1.0×10^9/L; 2) Hemoglobin =60 g/L (without red blood cell transfusion within 14 days); 3) Platelets =50×10^9/L; 4) Absolute lymphocytes (ALC) = 0.5×10^9/L; 5) Serum total bilirubin =1.5×upper limit of normal (ULN); 6) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5×ULN; 7) Creatinine 92% under non-oxygenation conditions; 9. Women of childbearing age must have a negative serum or urine pregnancy test report (women who have undergone surgical sterilization or women who are at least 2 years postmenopausal are not considered women of childbearing potential). Specific Inclusion Criteria: Relapsed and Refractory Systemic Lupus Erythematosus: 1.Comply with the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria; 2.In the moderate to severe active stage of the disease, SELENA-SLEDAI score >6; 3.And have at least one British Island Lupus Assessment Group Index (BILAG-2004) Category A (severe performance) or two Category B (moderate performance) organ scores, or both; 4.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide,tacrolimus,cyclosporine, and biological agents including rituximab, belimumab, tatacept, etc. Relapsed and Refractory Sjogren's Syndrome 1.Meet the 2002 AECG criteria or the 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome; 2.Definition of relapse and refractory: Conventional treatment is ineffective or disease activity reappears after remission. The definition of routine treatment: the use of glucocorticoids (more than 1 mg/Kg/d) and cyclophosphamide, and any one or more of the following immunomodulatory drugs for more than 6 months: antimalarial drugs, azathioprine, mycophenolate mofetil , methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents including rituximab, belimumab, tatacept, etc. Relapsed, Refractory/Progressive Diffuse Scleroderma 1.Comply with the 2013 ACR classification criteria for scleroderma and comply with diffuse manifestations; 2.Combined with interstitial pneumonia: chest HRCT shows interstitial changes with groun
Exclusion criteria
Exclusion criteria: 1.Have active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system; 2.Fungal, bacterial, viral or other infections exist or are suspected and are not controlled or require intravenous antibiotic treatment; simple urinary tract infections and uncomplicated bacterial pharyngitis are allowed; 3.Suffering from hepatitis B (hepatitis B virus surface antigen and hepatitis B DNA >1000 copies/ml) or hepatitis C (positive hepatitis C antibody test); syphilis infection (antibody positive); human immunodeficiency virus (HIV) infection; 4.Past medication: 1) CD19 targeted therapy; 2) Inject live vaccines within 4 weeks before enrollment; 3) Immunosuppressive antibodies (such as anti-CD20, anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor) used within 4 weeks before enrollment; 4) Use immunostimulatory or immune enhancer treatment (such as tacrolimus, cyclosporine, interferon-a, interferon-ß, IL-2) within the 5 half-lives before apheresis; 5) Have used systemic cytotoxic drugs within 2 weeks before enrollment, including daily or weekly low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, clotrexate or Melphalan, vincristine, etc.); 6) Long-acting growth factors within 14 days before apheresis (such as pegfilgrastim) or short-acting growth factors within 5 days before apheresis or drugs used for cell mobilization (such as granulocyte colony-stimulating factor/non- Gestin, Plexafor); 7) The use of pharmacological doses of corticosteroids (>10 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs must be avoided within 4 days before enrollment. 5.Have a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina or other clinically significant heart diseases within 12 months before enrollment; 6.History of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kosterman syndrome, Swachmann-Diamond syndrome, etc.; 7.History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to take prophylactic anticoagulant drugs; 8.Have suffered from other malignant tumors in the past or at the same time (except for basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix and other malignant tumors that have been effectively controlled without treatment in the past five years); 9.Use of other investigational pharmaceutical products within 30 days before screening; 10.Women of childbearing age who are pregnant or breastfeeding (because chemotherapy has potentially dangerous effects on the fetus or baby); 11.Male and female subjects who are unwilling to undergo birth control within 6 months from the signing of the informed consent form to the completion of the last administration of the study drug; 12.Any medical activity that may interfere with the evaluation of the safety or efficacy of the study; 13.According to the investigator's judgment, the subject is unlikely to complete all study visits or procedures required by the protocol, including follow-up visits or comply with the requirements for participation in the study; 14.Those who have used any CAR-T cell products or other genetically modified T cell therapies in the past. Specific Exclusion Criteria: Relapsed and Refractory
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity;Laboratory abnormalities and type, frequency and severity of adverse events;Proportion of patients for whom a CAR-T cell product could be prepared Percentage of subjects for whom the desired dose of anti-CD19 -CAR-T cells can be successfully manufactured; | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and grading of CRS and neurotoxicity;The level and persistence of anti-CD19-CAR-T cells in blood samples;Disease remission rate;Incidence of anti-CD19 antibodies;Cytokine levels in serum, including IL-6, IL-10, IFN-?, and TNF-a concentrations; | — |
Countries
China
Contacts
Public ContactLi Sun
The First Affiliated Hospital of Wenzhou Medical University
Outcome results
None listed