Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Neutrophil 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), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive a combined T cell depleted (TCD) haploidentical peripheral blood stem cell (PBSC) and unrelated umbilical cord blood transplantation (UCBT) using a total lymphoid irradiation (TLI) based preparative regimen.
Primary objective:
- To estimate the incidence of donor derived neutrophil engraftment by day +42 post-transplant for participants with high-risk hematologic malignancies undergoing a total lymphoid irradiation (TLI)-based hematopoietic cell transplantation (HCT) using a T cell depleted (TCI) haploidentical donor peripheral blood stem cell (PBSC) donor combined with an unrelated umbilical cord blood (UCB) donor.
Secondary objectives:
- Estimate the incidence of malignant relapse, event-free survival (EFS), and overall survival (OS) at one-year post-transplantation.
- Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) in the first 100 days after transplantation.
- Estimate the incidence of secondary graft failure transplant related mortality (TRM) and transplant related morbidity in the first 100 days after HCT.
详细描述
Prior to stem cell infusion, participants will receive a preparative regimen of total lymphoid irradiation (TLI), fludarabine, cyclophosphamide, melphalan, and thiotepa to prepare their bone marrow. Thereafter, they will receive a hematopoietic cell graft from a haploidentical donor and an unrelated umbilical cord blood donor. Post-transplantation immunosuppressive treatment will include tacrolimus and mycophenolate mofetil.
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
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Cyclophosphamide (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Thiotepa (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Fludarabine (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Melphalan (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Mesna (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: G-CSF (Biological)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Mycophenolate mofetil (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Tacrolimus (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Methylprednisolone (Drug)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Total lymphoid irradiation (Radiation)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Lymphocyte infusions (Biological)
Treatment
Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions.
Cells for infusion are prepared using the CliniMACS System.
干预措施: CliniMACS (Device)
结局指标
主要结局
Number of Participants With Neutrophil Engraftment
时间窗: Until day 42 post-transplant
Neutrophil engraftment is defined as absolute neutrophil count (ANC) recovery of ≥ 0.5 x 10\^9/L (500/mm\^3) for three consecutive laboratory values obtained on different days (derived from either donor). Date of engraftment is the date of the first of the three consecutive laboratory values. The number of patients engrafted by day +42 post-transplant is provided.
次要结局
- Number of Participants With Overall Survival (OS)(One year after transplantation)
- Number of Participants With Transplant-related Mortality (TRM)(100 days after transplantation)
- Number of Participants With Malignant Relapse(One year after transplantation)
- Number of Participants With Transplant-related Morbidity(100 days after transplantation)
- Number of Participants With Event-free Survival (EFS)(One year after transplantation)
- Number of Participants With Secondary Graft Failure(100 days after transplantation)
- Number of Participants by Severity With Acute Graft Versus Host Disease (GVHD) in the First 100 Days After HCT(100 days after transplantation)
- Number of Participants by Severity With Chronic Graft Versus Host Disease (GVHD) in the First 100 Days After HCT(100 days after transplantation)