Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
研究概览
简要总结
Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft-versus-host disease (GVHD).
To safeguard against GVHD, the investigators propose modifying T cells to encode a 'switch' so that they can be eliminated if problems arise.
Children receiving half-matched (haploidentical) transplants from a parent are most likely to benefit from this strategy. At present these patients receive blood stem cells from a parent, but the T cells are removed because the risk of serious GVHD is unacceptable. This means that they are much more likely to suffer from life threatening infections or experience a relapse of leukaemia. The investigators want to use gene therapy to produce "safe" T cells which can be used to strengthen the transplant and prevent these serious complications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with primary immunodeficiencies, haematological malignancies or metabolic disorders at GOSH (children of both sexes, aged 0 to 16 years) undergoing haploidentical transplant
- •Both patient and donor must give informed consent in writing.
- •The donor must be willing, able and available for donation of T cells by collection of whole blood or leukapheresis.
- •The patient should be free of serious intercurrent illness.
排除标准
- •Donor unfit or unavailable
- •Donor positive for Hepatitis B or C, or HTLV-1, or HIV
- •Patient receiving Ganciclovir, Aciclovir, Cidofovir a result of active CMV, adenovirus, varicella zoster or herpes simplex infection infection
- •GVHD ≥ grade II before infusion of gene modified T cells
- •Serious intercurrent illness
研究组 & 干预措施
HSVTK retrovirally-transduced donor T lymphocytes
HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD
- dose 1 5x104 cells/kg
- dose 2 5x105 cells/kg
干预措施: HSVTK retrovirally-transduced donor T lymphocytes (Biological)
结局指标
主要结局
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
时间窗: 12 months after final dose
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
次要结局
- Incidence of GvHD(12 months after final dose)
- Patient survival(12 months after final dose)