Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Determine the rate of GVHD after alpha beta TCR depletion
研究概览
简要总结
This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological confirmation of hematological malignancies
- •Acute leukemias
- •Acute Myeloid Leukemia (AML) and related precursor neoplasms
- •Favorable risk AML is defined as having one of the following:
- •Acute lymphoblastic leukemia (ALL)/lymphoma
- •Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features.
- •Age 60 years of age or younger at the time of consent
- •Karnofsky performance status ≥ 70% or Lansky play score 50% for ≤16 years of age.
- •Adequate organ function
排除标准
- •Pregnant or breastfeeding.
- •Active uncontrolled infection within 1 week of starting preparative therapy
- •Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR.
- •Any prior autologous or allogeneic transplant
- •CML blast crisis
- •Active central nervous system malignancy
研究组 & 干预措施
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Levetiracetam (Drug)
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Thymoglobulin (Drug)
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells (Biological)
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Thymoglobulin (Drug)
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Rituximab (Drug)
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Fludarabine (Drug)
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Melphalan (Drug)
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Fludarabine (Drug)
Arm 3B: ATG, Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
ATG/Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
干预措施: Busulfan (Drug)
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/CY/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/CY/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/CY/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Thymoglobulin (Drug)
Arm 5B: ATG, Cyclophosphamide (CY), Total Body Irradiation (TBI)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/CY/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Cyclophosphamide (Drug)
Arm 1A: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
干预措施: Busulfan (Drug)
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
干预措施: Rituximab (Drug)
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Fludarabine (Drug)
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Thymoglobulin (Drug)
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Busulfan (Drug)
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Busulfan (Drug)
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Cyclophosphamide (Drug)
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Fludarabine (Drug)
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
干预措施: Fludarabine (Drug)
Arm 2A: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen, Closed to Accrual
Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Busulfan (Drug)
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
干预措施: Melphalan (Drug)
Arm 1B: ATG, Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 3A: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. , Closed to Accrual
干预措施: Levetiracetam (Drug)
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Fludarabine (Drug)
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Rituximab (Drug)
Arm 2B: ATG, Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Patients will be treated on the most medically appropriate regimen with a preference for ATG/Flu/BU/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Levetiracetam (Drug)
Arm 4B: ATG, Busulfan (BU), Cyclophosphamide (CY)
Patients will be treated on the most medically appropriate regimen with a preference for ATG/BU/CY Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
干预措施: Thymoglobulin (Drug)
结局指标
主要结局
Determine the rate of GVHD after alpha beta TCR depletion
时间窗: 100 days
GVHD incidence after treatment.
次要结局
- Transplant engraftment(42 days)
- Overall survival (OS)(12 months)
- Non-relapse mortality (NRM)(12 months)
- Graft Failure(100 days)