CAR-T
Conditions
Brief 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.
Detailed description
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.
Interventions
DRUGGC012F injection
Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) once by intravenous infusion on Day 0.
Sponsors
Gracell Biotechnologies (Shanghai) Co., Ltd.
Zhejiang University
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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of subjects with DLT | Within 28 days after GC012F injection infusion | DLT definition is dose-limiting toxicity |
| The proportion of subjects with adverse events | Within 12 weeks after GC012F injection infusion | All adverse events were evaluated according to NCI-CTCAE v5.0 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving SRI-4 | 4, 8, 12 and 24 weeks after GC012F injection infusion | SELEAN-SLEDAI，BILAG，PGA |
| Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) | After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24] | Test method: flow cytometry and qPCR |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, MD
Outcome results
None listed