A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease
试验速览
- 阶段
- 1 期
- 入组人数
- 22
- 试验地点
- 5
- 主要终点
- Progression of graft versus host disease according to the 2014 NIH consensus criteria and myelosuppression after the administration of 3 doses of donor regulatory T cells / kg recipient's body weight: 0.5 x 10ˆ6, 1.0 x 10ˆ6 and 2.0-3.0 x 10ˆ6 cells
研究概览
简要总结
Phase 1/2 clinical study for the treatment of steroid-refractory chronic graft versus host disease after an allogeneic transplant of hematopoietic progenitors with donor CliniMACS-selected regulatory T cells
详细描述
Phase 1/2 clinical study evaluating safety (Phase 1) and preliminary efficacy (Phase 2) of donor regulatory T cells for patients with steroid-refractory chronic graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).
Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs.
Phase 1 clinical trial will include groups of 5 patients sequentially treated with: 0.5 x 10ˆ6, 1.0 x 10ˆ6, 2-3 x 10ˆ6 donor Treg/kg. Phase 2 clinical trial will include another 5 to 10 patients treated with MTD.
Donor Treg will be selected by the following sequential steps:
-
- negative depletion of CD8 and CD19 cells
-
- positive selection of CD25 cells
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs.
- •Stable immunosuppressive medication in the 4 weeks prior to initiation of treatment
- •PS 0-2 ECOG
- •Adequate liver, kidney, lung and hematopoietic system functions
排除标准
- •Pediatric patients
- •Pregnant women
- •Ongoing prednisone requirement >1 mg/kg/day (or equivalent)
- •Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)
- •New immunosuppressive medication in the 4 weeks prior
- •Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior
- •Exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior
- •Donor lymphocyte infusion within 100 days prior
- •Active malignant relapse
- •Active uncontrolled infection
- •HIV-infected patients
研究组 & 干预措施
Administration of 0.5 x 10ˆ6 donor Treg/kg
First group of 5 patients will receive a total of 0.5 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.
干预措施: Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease (Biological)
Administration of 1.0 x 10ˆ6 donor Treg/kg
Second group of 5 patients will receive a total of 1.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.
干预措施: Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease (Biological)
Administration of 2.0-3.0 x 10ˆ6 donor Treg/kg
Third group of 5 patients will receive a total of 2.0-3.0 x 10ˆ6 donor Treg/kg. Part of Phase 1 study.
干预措施: Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease (Biological)
Administration of MTD of donor T reg
Preliminary Phase 2 study will include another 5 to 10 patients at the MTD identified in the Phase 1 study
干预措施: Donor regulatory T cell adoptive immunotherapy in chronic graft versus host disease (Biological)
结局指标
主要结局
Progression of graft versus host disease according to the 2014 NIH consensus criteria and myelosuppression after the administration of 3 doses of donor regulatory T cells / kg recipient's body weight: 0.5 x 10ˆ6, 1.0 x 10ˆ6 and 2.0-3.0 x 10ˆ6 cells
时间窗: Response evaluated 12 weeks after infusion
Progression of graft versus host disease and myelosuppression are indicators of toxicity and MTD associated with the infusion of donor regulatory T cells
次要结局
- Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells(Response evaluated 12 weeks after infusion)
- Total lymphocyte, CD4, CD8 and regulatory T cell counts after the infusion of donor regulatory T cells for the treatment of chronic graft versus host disease(Response evaluated 12 weeks after infusion)
- Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease(Response evaluated 12 months after infusion)
研究者
Joao F. Lacerda
MD PhD, Associate Professor of Medicine
Instituto de Medicina Molecular João Lobo Antunes