A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Evaluation the safety of CAR-T-cell treatment
研究概览
简要总结
To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody.
详细描述
This study is a prospective, single-center, single-arm, open-label and phase I clinical trial. Subjects with CD4+T cell counts greater than 350/μl and viral loads of <50 copies/ml over 1 year by antiviral treatment are enrolled. T cells are stimulated with CD3 and CD28, transduced with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody and expanded for approximately 2 weeks. Then, patients are infused with CAR T cells at a dosage of 1×10^5 CAR-T cells/kg body weight. If this dose is well tolerated, dosing will be increased to 5×10^5 CAR T cells/kg body weight. After infusion, adverse events, and HIV-1 latent reservoir size and CAR levels in peripheral blood will be monitored to assess the safety of CAR-T-cell treatment, potential therapeutic efficacy and kinetics of CAR T cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 70 years
- •HIV-1 infection by confirmed test;
- •Receiving antiviral treatment ≥ 1 years;
- •Current CD4+ T cell count > 350 cells/μl;
- •HIV-1 RNA levels of < 50 copies/ml for at least a year;
- •Patients who agrees to use two effective methods of contraception to avoid pregnancy during the study period.
- •Patients who sign the informed consent form prior to inclusion in the study.
排除标准
- •Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection;
- •A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment;
- •A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years;
- •Participants with clinically significant laboratory abnormalities as follows:
- •Hemoglobin ≤ 10 gm/dl (female), <11g/dl (male)
- •Absolute neutrophil count ≤ 1×10^9/L
- •Platelet count ≤100×10^9/L
- •Alanine aminotransferase (ALT)≥ 2.5 x ULN
- •Aspartate aminotransferase (AST) ≥ 2.5 x ULN
- •Total bilirubin > 1.5 ULN
- •Serum creatinine >110 μmol/L
- •International normalized ratio (INR) >1.5 or activated partial thromboplastin time (APTT) >45 s
- •Patients with severe psychiatric illness, drugs or alcohol abuse;
- •A woman who is in pregnancy or lactation;
- •A history of central nervous system disease, such as cerebral hemorrhage, dementia, epilepsy and autoimmune diseases;
- •Patients with a non-AIDS-related serious underlying disease;
- •Patients who participate in another clinical study currently which may affect the results of this study.
研究组 & 干预措施
CAR-T-cell therapy
Four patients with plasma HIV RNA <50 copies/ml and CD4+T cell count more than 350 cells/μl receiving at least one-year antiviral treatment are injected intravenously with 1×10^5 CAR-T cells/kg body weight. If the dosage of 1×10^5 CAR-T cells/kg body weight is well tolerated, 5×10^5 CAR-T cells/kg body weight will be infused for another 4 subjects who meet the inclusion and exclusion criteria.
干预措施: CAR-T cells (Biological)
结局指标
主要结局
Evaluation the safety of CAR-T-cell treatment
时间窗: 3 months
To assess the adverse events of CAR-T-cell therapy in HIV-1 infected individuals by measuring liver function, blood routine, and cytokine and so on in this clinical trial
次要结局
- Assessment the potential therapeutic efficacy of CAR-T cell therapy(3 months)