Safety and Feasibility Study of Allotransplantation of CRISPR/Cas9 CCR5 Gene Modified CD34+ Hematopoietic Stem/Progenitor Cells in HIV-infected Subjects With Hematological Malignances
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Persistence of CCR5 gene disruption in engrafted cells
研究概览
简要总结
The investigators performed this study to evaluate the safety and feasibility of transplantation with CRISPR/Cas9 CCR5 gene modified CD34+ hematopoietic stem/progenitor cells for patients that develop AIDS and hematological malignances. Patients will be treated with antiviral therapy (ART) to achieve undetectable HIV-1 virus in peripheral blood before conditioning. CD34+ cells from donors will be infused into the patients after treatment with CRISPR/Cas9 to ablate CCR5 gene.
详细描述
The primary objective of this study is to determine the safety of the infusion of CD34+ cells which are treated with CRISPR/Cas9 to disrupt the CCR5 gene. The secondary objective is to evaluate the resistance to HIV-1(R5) in infected patients after infusion of modified CD34+ cells with or without an antiretroviral therapy interruption (ATI). After the transplantation, the reconstitution time and frequency of multi-lineage hematopoietic cell will be analyzed against previously reported HSCT in HIV-1 patients. After the detection of high CD4+ T cells reconstitution (over 600 cells/μL) and CCR5 negative cells (over 1%) in peripheral blood, subjects will undergo an ATI. HIV-1 RNA level and CD4+ cell counts will be monitored biweekly for at least one month.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 to 60, male of female;
- •Hematological neoplasms;
- •HIV-1 R5 tropic virus with no CXCR4-tropic or R5/X4 dual-tropic HIV;
- •On ART with undetectable HIV-1 level (<40gc/ml, HIV-1 RNA);
- •Availability of a consenting HLA-matched donor;
- •No cardiomyopathy or congestive heart failure;
- •CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL;
- •Absence of psychosocial conditions and be willing to comply with study-mandated evaluations for 2 years;
- •Life expectancy of at least 1 year.
排除标准
- •Acute or chronic hepatitis B or hepatitis C infection;
- •Any cancer or malignancy other than hematological neoplasms;
- •Subject with CMV retinitis or other active CMV infection related diseases;
- •Subject with organ dysfunction;
- •Non-pregnant and non-nursing;
- •Drug or alcohol abuse or dependence;
- •Currently enrolled in another clinical trial or underwent cell therapy;
- •Donor incapable for HSPC mobilization;
- •in the opinion of the site investigator, would interfere with adherence to study requirements.
结局指标
主要结局
Persistence of CCR5 gene disruption in engrafted cells
时间窗: 12 months
Participants will be transplanted with CD34+ cells which are treated using the CRISPR/Cas9 system to disrupt CCR5 gene. The persistence of CCR5 gene disruption in engrafted cells will be evaluated by sequencing.
次要结局
- CD34+ cell number(the first month)
研究者
Chen Hu
Study Director
Affiliated Hospital to Academy of Military Medical Sciences