Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
研究概览
简要总结
The investigators have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. The investigators thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
详细描述
We have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. We thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
dDLI is administered after failure of 1 or several previous stdDLI of at least 107 CD3+ cells/kg, defined after a minimal follow-up of 2 months after the last injection. The absence of previous clinical manifestations of GVHD is required to be included. To prepare dDLI, CD25+ Treg are depleted from donor leukaphereses using anti-CD25 magnetic microbeads and a CliniMACS device (MYLTENYI). In order to evidence the potential effect of dDLI, the dDLI cell dose is adjusted to be below or equal to the maximal cell dose previously received in stdDLI. No comparison is planned in the analysis.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hematological malignancy except chronic myeloid leukaemia.
- •Previous allogeneic hematopoietic stem cell transplantation.
- •Relapse diagnosed at the molecular, cytogenetic, or cytological level.
- •Failure of a previous stdILD or inclusion in first intention if progressive disease.
- •Age > 18 years and < 70 years at the time of inclusion.
- •Performance status considered on the score ECOG <
- •Life expectation 1-month-old superior.
- •Signed written informed consent.
- •Negative HCG in the 7 days preceding the inclusion for women in age of procreation.
- •Membership of the French national insurance.
排除标准
- •Chronic myeloid leukemia
- •Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
- •Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
- •Dysfunction of liver (ALAT/ASAT > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
结局指标
主要结局
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
时间窗: 4 weeks after dDLI
次要结局
- The incidence of GVHD of any grade after dDLI(during the 12 months)
- The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy(during the 12 months)
- The survival and the survival without disease after dDLI(during the 12 months)