phase i clinical study of gc012f injection in treatment of refractory systemic lupus erythematosus

Conditions: CAR-T

Summary: this is a phase i, single arm, non-randomized, open label, treatment study trial to determine the recommended phase ii dose of gc012f injection (cd19-bcma car-t cells) in patients with refractory systemic lupus erythematosus.

systemic lupus erythematosus (sle) is a kind of autoimmune diseases mediated by autoantibody-forming immune complexes, which involving multiple systems and organs. autoreactive b cells can self-activate and differentiate into plasma cells releasing large amounts of autoantibodies, while they can also present their own antigens to autoimmune t cells, thus activating t cells and promoting the release of inflammatory factors. traditional sle treatment aims at long-term remission, while, cd19- bcma car-t cells can theoretically completely deplete abnormal antibody-producing b cells, allowing immune rebuilding and restoring the patient's normal immune function, achieving drug-free survival, which fully reflects the application prospects of car-t therapy in sle.

Eligibility criteria:
inclusion criteria: 1. 18-70 years old; 2. total score ≥ 10 on the eular/acr 2019 sle classification criteria; 3. selena-sledai≥8; 4. patients with cd19+ b-cell; 5. active organ involvement; 6. hemoglobin≥85 g/l; 7. wbc≥2.5×10\^9/l 8. neut≥1×10\^9/l; 9. plt≥50×10\^9/l; 10. ast/alt below 2 times the upper limit of normal; creatinine clearance ≥30 ml/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%; 11. adequate venous access for apheresis, and no other contraindications for leukapheresis; 12. women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. subjects agree to take effective contraceptive measures during the trial until at least 1 year after car-t cells infusion. 13. agree to attend follow-up visits as required; 14. voluntary participation and informed consent signed by the patient or his/her legal/authorized representative; exclusion criteria: 1. renal disease: severe lupus nephritis (serum creatinine \> 2.5 mg/dl or 221 μmol/l) within 8 weeks prior to leukapheresis, or subjects who need prohibited drugs to treat active nephritis or subjects who need hemodialysis; 2. cns disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident \[cva\], encephalitis or cns vasculitis, psychiatric patients with depression or suicidal thoughts; 3. patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system; 4. patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers; 5. received immunosuppressive therapy within 1 week prior to leukapheresis; 6. patients with hiv infection; active infection of hepatitis b virus or hepatitis c virus; patients with syphilis infection; 7. the presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening; 8. received live vaccine treatment within 4 weeks prior to screening; 9. severe allergies or hypersensitivity; 10. contraindication to cyclophosphamide in combination with fludarabine; 11. subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion; 12. cannula or drainage tubes other than central venous catheters; 13. pregnant or lactating women, or subjects who plan to have children within 1 year of treatment; 14. subjects with prior cd19 or bcma-targeted therapy 15. participated in any clinical study within 3 months prior to enrollment 16. any situations that the investigator believes the patients are not suitable for the study.