Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Number of Transplant Recipients With Successful Engraftment
研究概览
简要总结
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells.
The investigators anticipate enrollment of 75 donors and 75 recipients.
PRIMARY OBJECTIVE:
- To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy.
SECONDARY OBJECTIVES:
- Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
- Estimate incidence and severity of acute and chronic (GVHD).
- Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
详细描述
Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK).
The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts.
Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Total Lymphoid Irradiation (Radiation)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Fludarabine (Drug)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Cyclophosphamide (Drug)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Thiotepa (Drug)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Melphalan (Drug)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: HPC,A Infusion (Biological)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: TC-NK Infusion (Biological)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: G-CSF (Biological)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Mesna (Drug)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: CliniMACS (Device)
Transplant Recipients
Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Mycophenolate mofetil (Drug)
结局指标
主要结局
Number of Transplant Recipients With Successful Engraftment
时间窗: 42 days post engraftment
Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.
次要结局
- Number of Transplant Recipients With Malignant Relapse(One-year post-transplantation)
- Overall Survival(one year post-transplantation)
- Event-free Survival(One year post-transplantation)
- Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)(100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .)
- Severity of Chronic Graft Versus Host Disease (cGVHD)(1 year post-transplant for chronic GVHD .)
- Number of Transplant Recipients With Transplant-related Mortality (TRM)(In the first 100 days after transplantation)
- Severity of Acute Graft Versus Host Disease (aGVHD)(100 days post-transplant for acute GVHD.)