A Pilot Study to Evaluate Efficacy and Safety of Multiplexed shRNA-modified CD34+ Cells in HIV-infected Patients.
试验速览
- 阶段
- 1 期
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Adverse side effects
研究概览
简要总结
The purpose of the study is to evaluate the efficacy and safety of autologous CD34+ cells that stably express multiplexed shRNA to treat HIV infection.
详细描述
CD34+ cells will be isolated from mobilized PBMC of HIV patients. The cells will be lentivirally transduced with multiplexed shRNAs in the same vector that target CCR5 and HIV genome. Such modified cells will be infused back to the patients who have received bulsufan preconditioning before infusion. The patients will then be evaluated for efficacy and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index (BMI) from 18 - 25; body weight ≥50kg.
- •Diagnosis of HIV infections/AIDS based on "Diagnostic Criteria for HIV/AIDS" WS 293-
- •No antiretroviral therapy (ART) in the past 6 weeks and refuse to receive ART.
- •CD4 T cell count ≥350/μl.
- •No plan for pregnancy in the near future and agree to practice non-drug based contraception.
- •Voluntary to participate in the study, comply with the study design to complete all monitory measurements, and agree to sign the study agreement.
排除标准
- •Existence of infections/opportunistic tumors.
- •Mutations in the shRNA target sequences.
- •White blood cell count <3x10^9/L, neutrophil count <1.5x10^9/L, hemoglobin <110g/L, platelet count <100x10^9/L.
- •Liver diseases (HBV, chronic HCV infection, congenital liver metabolic disease), abnormal liver functions (test value 2x above normal).
- •Kidney deficiency (Creatinine level above the upper limit of normal levels).
- •Severe chronic disease, metabolic disease (e.g., diabetes), neurological and psychiatric diseases.
- •History of pancreatitis.
- •Women in pregnancy, lactating or at reproductive age who do not practice contraception.
- •Allergy to agents or drugs used in the study.
- •Verified or suspected abuse of alcohol and drugs.
- •Participated in other clinical trials within 3 months.
- •Based on investigator's assessment, those who are unfit for the study (e.g., general weakness, poor compliance with study design).
- •Personal or family history of tumors.
研究组 & 干预措施
No busulfan preconditioning
shRNA-modified CD34+ cells without busulfan preconditioning.
干预措施: shRNA-modified CD34+ cells (Biological)
Low dose busulfan preconditioning
shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.
干预措施: shRNA-modified CD34+ cells (Biological)
Low dose busulfan preconditioning
shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.
干预措施: Low dose busulfan preconditioning (Drug)
High dose busulfan preconditioning
shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.
干预措施: shRNA-modified CD34+ cells (Biological)
High dose busulfan preconditioning
shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.
干预措施: Busulfan preconditioning (Drug)
结局指标
主要结局
Adverse side effects
时间窗: 18 months
Patients will be monitored for any signs of adverse effects.
次要结局
- Efficacy of treatment(18 months)
研究者
Hongzhou Lu
professor
Shanghai Public Health Clinical Center