Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID): Selective Depletion of Naive Cells From the Graft
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Number of death
研究概览
简要总结
The purpose of this study is to evaluate selective depletion of naïve CD45RA+ T cells from allogenic peripheral blood stem cell graft in children transplanted for combined immune deficiency. The aims of this procedure are to prevent graft versus host disease (GVHD) while preserving anti-infectious response from donor memory T lymphocytes.
详细描述
Combined immunodeficiencies (CIDs) are an heterogeneous group of primitive immunodeficiency (PID), which affect T cells development, function or both. These inherited conditions can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). These procedures have a high risk of morbidity and mortality such a graft versus host disease (GVHD), rejection of the graft and serious infections, especially in this population of children with PID. GVHD is more frequent and severe if the donor is not an identical sibling and/or presents an HLA-mismatch. GVHD requires high immunosuppression as prevention and treatment, and therefore impedes immunity against infections.
In vitro and animal models suggest that GVHD is mediated by naïve T cells. The aim of this study is to decrease the rate and severity of GVHD after selective depletion of naïve CD45RA+ T cells from allogeneic hematopoietic stem cell grafts in patients with CIDs with high risk of severe GVHD, and to preserve immunity against pathogens in a population with high vulnerability to infections.
The project aims is, first, to show improvement of rejection-free and GVH-free survival 12 months post-transplant, and secondly, to show the decrease of viral infection, and assess immune reconstitution kinetic and quality and specific antiviral responses, after a engraftment with naïve cell depleted allograft.
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
- 12 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient from 12 months to 18 years
- •Combined immunodeficiencies with known molecular diagnosis or if unknown, corresponding of p-CID study's definition
- •Hematopoietic stem cell Transplantation planned with one of the following donors :
- •sibling with 1 or 2 HLA antigens mismatch
- •parent 10/10 or 9/10 identical
- •unrelated donor: 10/10 or 9/10 identical
- •Consent form signed by the child's legal guardian
- •Patient using effectiveness contraception during this trial
- •Affiliated or beneficiary of a health insurance regimen
排除标准
- •Wiskott-Aldrich syndrome
- •Ongoing pregnancy
- •Positive HIV PCR
- •Contraindication for hematopoetic stem cell transplantation
- •Geno-identical donor in the siblings
- •hematopoetic stem cell transplantation antecedent
研究组 & 干预措施
Treatment
干预措施: Depletion in CD45RA graft donor (Biological)
结局指标
主要结局
Number of death
时间窗: 12 months after the transplantation
Number of graft rejection
时间窗: 12 months after the transplantation
Number of graft versus host disease (GVHD) grade III or IV
时间窗: 12 months after the transplantation
次要结局
- T Lymphocyte proliferations to phytohemagglutinin (PHA)(12 months after the transplantation)
- Need of antiviral treatment(12 months after the transplantation)
- Proportion of T CD4 and CD8 lymphocytes specific of cytomegalovirus, Epstein Barr virus and adenovirus(12 months after the transplantation)