Autoimmune Diseases
Conditions
Brief summary
This study is a single-center, open-label, single-dose exploration clinical trial for treating patients with partially relapsed/refractory autoimmune diseases by infusing FIT-(BCMA+CD19)-CAR-T cells after pre-treatment with cleansing therapy. In this study phase, a traditional "3+3" trial design is employed for dose escalation.
Detailed description
This study intends to include some patients with relapsed/refractory autoimmune diseases. The subjects will undergo single infusion of FIT-(BCMA+CD19)-CAR-T cells after undergoing screening, collection of peripheral blood mononuclear cells (PBMC), and pre-treatment with conditioning chemotherapy. Apart from the baseline period, the time points for evaluating the therapeutic efficacy of the subjects after treatment are the 1st、2nd、3rd、6th、9th and 12th month after infusion, until disease progression (PD), relapse, change of treatment regimen, death, intolerable toxicity, at the discretion of the investigator, or voluntary withdrawal by the patient (whichever occurs first). Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Safety of FIT-(BCMA+CD19)-CAR-T cell therapy will be evaluated through laboratory tests, 12-lead electrocardiograms, vital signs, physical examinations, etc. Blood samples will be collected from subjects to assess cellular pharmacokinetics and explore the effects of cellular drugs on ferritin, C-reactive protein, and related cytokines.
Interventions
BIOLOGICALFIT-(BCMA+CD19)-CAR-T Cells
Before cell infusion, researchers may decide, based on necessity, whether to administer prophylactic medication, which may include options such as acetaminophen and diphenhydramine, or H1 antihistamines, among others. Subjects are allowed to receive adequate supportive care after FIT-(BCMA+CD19)-CAR-T cells infusion, including blood transfusions and blood products, antibiotic therapy, antiemetics, antidiarrheals, analgesics, etc.
Sponsors
Beijing Boren Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation in the clinical study, with the subject or their legally authorized representative fully understanding and providing written informed consent (ICF) for this study, and willingness to comply with and complete all trial procedures. 2. Aged 18 to 70 years. 3. ECOG performance status ≤ 2. 4. Life expectancy of at least 12 weeks. 5. Adequate venous access for apheresis and no other contraindications to blood cell separation. 6. Laboratory parameters at screening must meet the following requirements, with no receipt of cell growth factors within 7 days (or 2 weeks for long-acting formulations) prior to the screening hematology assessment: Absolute neutrophil count ≥ 1.0 × 10⁹/L. Hemoglobin ≥ 60 g/L (without red blood cell transfusion within 14 days). Platelet count ≥ 50 × 10⁹/L (thrombocytopenia due to autoimmune disease may be excluded at the investigator's discretion). Absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (acute elevations due to autoimmune disease may be excluded at the investigator's discretion). Creatinine clearance (Cockcroft-Gault formula) ≥ 30 mL/min. 7. Cardiac ejection fraction ≥ 45%, no pericardial effusion (excluding minimal or physiological effusion) confirmed by echocardiography (ECHO), and no clinically significant findings on electrocardiogram (ECG). 8. Baseline oxygen saturation \> 92% while breathing room air. 9. Female subjects of childbearing potential must have a negative serum or urine pregnancy test (women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of childbearing potential). 10. Male and female subjects willing to practice contraception from the time of signing the ICF until 12 months after the last dose of study drug.
Exclusion criteria
1. Active central nervous system (CNS) disease, such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. 2. Presence or suspicion of fungal, bacterial (including but not limited to Mycobacterium tuberculosis), viral, or other infection that is uncontrolled or requires intravenous antifungal, antibacterial, or antiviral therapy; uncomplicated urinary tract infection and uncomplicated bacterial pharyngitis are permitted. 3. Hepatitis B (positive for hepatitis B surface antigen \[HBsAg\] with HBV DNA \> 1000 copies/mL), hepatitis C (positive for hepatitis C antibody), syphilis infection (positive for antibody), or human immunodeficiency virus (HIV) infection. 4. Prior or concomitant medication: Prior use of any CAR-T cell product or other genetically modified T-cell therapy. History of CD19-targeted therapy. Receipt of live vaccine within 4 weeks before enrollment. Use of another investigational medicinal product within 30 days before screening. Receipt of biologic macromolecular drugs (e.g., rituximab, belimumab, telitacicept, adalimumab, etanercept, etc.) that have therapeutic effects on the target indication within 4 weeks or 5 half-lives before enrollment. Receipt of \> 20 mg/day of prednisone or equivalent doses of other corticosteroids within 2 weeks before enrollment. Receipt of conventional synthetic disease-modifying drugs (e.g., cyclophosphamide, methotrexate, leflunomide, sulfasalazine, etc.) that have therapeutic effects on 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 associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, Schwachman-Diamond syndrome, etc. 7. History of lymphoproliferative disease or malignancy (except for basal cell carcinoma of the skin, in situ carcinoma of the breast/cervix, and other diseases that are disease-free and have not been treated within the past five years). 8. Women of childbearing potential who are pregnant or breastfeeding. 9. Any medical activity that may interfere with the evaluation of study safety or efficacy. 10. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up, or to comply with the requirements for study participation. Specific Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity | Up to 28 days from CAR-T infusion | The proportion of patients receiving CAR-T cells who encounter dose-limiting toxicities (DLTs). Safety evaluations are performed in accordance with the NCI-CTCAE version 5.0 standards (Cytokine Release Syndrome and neurotoxicity will be graded based on ASTCT/ASBMT grading criteria). |
Countries
China
Outcome results
None listed