Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients

Summary

This is an early exploratory phase, single arm, non-randomized, open label, treatment study trial to determine the maximum tolerated dose of GC012F injection (CD19-BCMA CAR-T cells) in patients with refractory systemic lupus erythematosus.

Eligibility

Inclusion Criteria:

1. 18-70 years old;
2. Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;
3. LLDAS response criteria are not achieved after administration with at least two immunosuppressants (including, but not limited to, azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, ciclosporin and iguratimod) and/or at least one approved biological agent for more than 6 months.
4. SELENA-SLEDAI≥8;
5. Patients with CD19+ B-cell;
6. Hemoglobin≥85 g/L;
7. WBC≥2.5×10\^9/L
8. NEUT≥1×10\^9/L;
9. BPC≥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 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. Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS\>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer;
17. Any situations that the investigator believes the patients are not suitable for the study.

Conditions2

Interventions1

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