ANCA Associated Vasculitis, Antiphospholipid Syndrome, Inflammatory Myopathy, Sjogren's Syndrome, Systemic Lupus Erythematosus (SLE), Systemic Sclerosis
Conditions
Keywords
CAR T, CD19, Autoimmune Diseases
Brief summary
This is an investigator-initiated trial to evaluate the safety and efficacy of anti- CD19-CAR-T cells in the relapse or refractory autoimmune diseases.
Detailed description
This is an investigator-initiated trial to evaluate the safety and efficacy of anti- CD19-CAR-T cells in the relapse or refractory autoimmune diseases. Study intervention consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Interim analysis will be performed when the last participant finishes the visit of 12 weeks after CAR-T cells infusion.
Interventions
BIOLOGICALanti-CD19-CAR-T cells
The subjects received infusions of anti-CD19 CAR-T cells following completion of lymphodepleting preconditioning chemotherapy. Dosage：1×10\^5 cells/Kg; 3×10\^5 cells/Kg; 1×10\^6 cells/Kg frequency：single infusion
Sponsors
Shanghai First Song Therapeutics Co., Ltd
First Affiliated Hospital of Wenzhou Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Common 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 \<1.5×ULN and endogenous creatinine clearance ≥60 mL/min. 7. The cardiac ejection fraction is ≥45%, echocardiography (ECHO) confirms that there is no pericardial effusion (except for a small amount or physiological), and the electrocardiogram results have no clinical significance; 8. Baseline oxygen saturation \>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). Common
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-α, interferon-β, 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 inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity | Up to 28 days from CAR-T infusion | Percentage of patients receiving CAR-T cells who experience dose-limiting toxicities (DLTs). |
| Laboratory abnormalities and type, frequency and severity of adverse events | Up to1 year from CAR-T infusion | Safety assessments are conducted using the NCI-CTCAE version 5.0 standards (CRS and neurotoxicity will be graded according to ASTCT/ ASBMT grading criteria) |
| Proportion of patients for whom a CAR-T cell product could be prepared | Up to 4 days from apheresis | Percentage of subjects for whom the desired dose of anti-CD19 -CAR-T cells can be successfully manufactured |
Countries
China
Contacts
Primary ContactJianxin Tu, Master's
Outcome results
None listed