Phase I Clinical Study of GC012F Injection in Treatment of Refractory Systemic Lupus Erythematosus
Overview
- Phase
- Phase 1
- Intervention
- GC012F injection
- Conditions
- CAR-T
- Sponsor
- Zhejiang University
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- The proportion of subjects with DLT
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
He Huang
Professor
Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •18-70 years old;
- •Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;
- •SELENA-SLEDAI≥8;
- •Patients with CD19+ B-cell;
- •Active organ involvement;
- •Hemoglobin≥85 g/L;
- •WBC≥2.5×10\^9/L
- •NEUT≥1×10\^9/L;
- •PLT≥50×10\^9/L;
- •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%;
Exclusion Criteria
- •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;
- •CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident \[CVA\], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts;
- •Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system;
- •Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
- •Received immunosuppressive therapy within 1 week prior to leukapheresis;
- •Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection;
- •The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening;
- •Received live vaccine treatment within 4 weeks prior to screening;
- •Severe allergies or hypersensitivity;
- •Contraindication to cyclophosphamide in combination with fludarabine;
Arms & Interventions
GC012F injection (CD19-BCMA CAR-T cells)
Dose level： DL1：1±20%×10\^5/kg, DL2：2±20%×10\^5/kg DL3：3±20%×10\^5/kg
Intervention: GC012F injection
Outcomes
Primary Outcomes
The proportion of subjects with DLT
Time Frame: Within 28 days after GC012F injection infusion
DLT definition is dose-limiting toxicity
The proportion of subjects with adverse events
Time Frame: Within 12 weeks after GC012F injection infusion
All adverse events were evaluated according to NCI-CTCAE v5.0 criteria
Secondary Outcomes
- Proportion of subjects achieving SRI-4(4, 8, 12 and 24 weeks after GC012F injection infusion)
- 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])