F01 in the Treatment of Moderate-to-severe Refractory Systemic Lupus Erythematosus

Exclusion Criteria

• •1. Known allergies, hypersensitivity, intolerance, or contraindications to F01 or any ingredient of drugs that may be used in the study (including fludarabine, cyclophosphamide, tocilizumab), or subjects who have had severe allergic reactions in the past.
• •2. Severe lupus nephritis (defined as urine protein \>6g/24 hours or serum creatinine \>2.5mg/dL or 221μmol/L) within 3 months prior to screening, or requiring active nephritis with drugs prohibited by the protocol, or requiring hemodialysis or treatment with prednisone ≥100mg/d or equivalent glucocorticoids ≥for 14 days.
• •3. Previous history or pathological changes of clinically significant central nervous system disease, including but not limited to lupus encephalopathy, seizures, cerebrovascular accident (ischemia/hemorrhage), dementia, cerebellar disease, organic encephalopathy syndrome, encephalitis, central nervous system vasculitis, or psychiatric disease.
• •4. Combined with severe pulmonary diseases, such as pulmonary hypertension with World Health Organization functional classification ≥ level 3, requiring oxygen therapy with an oxygen storage mask or non-invasive or invasive ventilator to assist breathing at screening;
• •5. Unstable cardiovascular function:
• •1. Myocardial infarction within 6 months prior to screening;
• •2. Unstable angina within 3 months prior to screening;
• •3. Uncontrolled, clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• •4. Mobitz type II. second-degree or third-degree atrioventricular block;
• •5. New York Cardiac Function Association Class ≥ 3 congestive heart failure;
• •6. Poorly controlled hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg) or concomitant hypertensive crisis or hypertensive encephalopathy;
• •6. Patients with a history of concomitant malignancy, including tumor-associated polymyositis/dermatomyositis. Patients with non-melanoma skin cancer, carcinoma in situ of the cervix, local prostate cancer, low-stage bladder cancer, ductal carcinoma in situ, or patients who have no evidence of recurrence in the past 2 years and do not need treatment are excluded.
• •7. Uncontrolled active bacterial, viral, fungal, mycobacterial infection or other infections requiring treatment with intravenous antibiotics, antiviral or antifungal drugs within 14 days prior to drenching conditioning chemotherapy; However, these drugs can be used for prophylactic treatment (including intravenous use).
• •8. Risk of active tuberculosis at screening, regardless of completion of adequate treatment, including the presence of signs or symptoms of active tuberculosis (such as fever, cough, night sweats, and weight loss) as judged by the investigator at screening; Chest imaging (e.g., chest x-ray, chest CT scan) documented at screening or at any time within 6 months prior to screening showing active tuberculosis; Evidence of latent tuberculosis infection, such as a positive γ-interferon release test, at screening.
• •9. Active hepatitis B virus (HBV), hepatitis C virus (HCV) infection at screening. Subjects who are HBsAg positive and/or HBcAb positive but HBV-DNA negative, and/or HCVAb positive but HCV-RNA negative are allowed to be enrolled (if the site report includes a range of reference values, the upper limit of normal for HBV-DNA and HCV-RNA tests is based on the test values of each site, and higher than the upper limit of test values is defined as \"positive\"; If the site report only shows \"negative/positive\", the positive is based on the test report result).
• •10. Known serum HIV virus antibody positivity or history of active HIV infection, as well as syphilis antibody positive.
• •11. Received the following treatments within the prescribed time frame prior to drenching conditioning chemotherapy:
• •1. Received autologous/allogeneic hematopoietic stem cell transplantation within 3 months;
• •2. Received ultraviolet radiation therapy within 6 weeks;
• •3. Received macromolecule therapy (excluding anti-CD20 monoclonal antibodies) within 4 weeks or 3 half-lives (whichever is longer); Received anti-CD20 monoclonal antibody therapy within 4 weeks;
• •4. Received small molecule targeted therapy within 2 weeks or 3 half-lives (whichever is longer);
• •5. Major surgery or live vaccination within 4 weeks;
• •6. Received a trial treatment within 4 weeks (except in the definitive placebo control group);
• •12. Pregnant or lactating women.
• •13. Use of concomitant medications/concomitant treatments expressly prohibited by the protocol during the screening period.
• •14. Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the opinion of the investigator, may affect the subject\'s safety or study compliance.