Double Umbilical Cord Blood Transplantation for Patients With Malignant and Non-Malignant Disorders
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Graft Failure Rate
研究概览
简要总结
The purpose of this study is to determine the safety and toxicity and feasibility of double umbilical cord blood transplantation (DUCBT) in patients with selected malignant and non-malignant, and to quantify the percentage and donor sources of mixed donor chimerism following DUCBT in patients with selected malignant and non-malignant disorders.
详细描述
Allogeneic stem cell transplantation from an human leukocyte antigen (HLA) matched related family donor is the treatment of choice for a wide variety of malignant and non-malignant disorders. Unfortunately, only 25% of potential recipients have an HLA matched related family donor, leaving approximately 75% of potential recipients requiring alternative sources of HLA matched allogeneic stem cells. One potential source of HLA matched allogeneic stem cells is from unrelated adult donors that have been identified in the national and international donor registries. However, several limitations restrict the uniform utilization of unrelated allogeneic adult donors including ethnic background of the recipient, acuity and timing of planned allogeneic transplant, availability of donor, and high risk of severe acute graft-versus-host disease (GVHD) (III/IV), among others. The investigators have recently identified a new alternative source of allogeneic stem cells, unrelated cryopreserved placental/cord blood stem cells.
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 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be eligible for double cord blood stem cell transplant (TNC ≥ 4x107/kg of two combined units) if available single cord blood has TNC ≤4.0 x 107/kg and they lack a matched (5-6/6) family donor, a 10/10 unrelated adult donor, and/or if their disease status required emergent stem cell transplant and they could not wait 2-3 months for searching for a matched unrelated adult donor.
- •Adequate renal function defined as:Serum creatinine <1.5 x normal, or Creatinine clearance or radioisotope glomerular filtration rate (GFR) >60 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
- •Adequate liver function defined as:Total bilirubin <1.5 x normal, or serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) <3.0 x normal
- •Adequate cardiac function defined as:Shortening fraction >27% by echocardiogram, or Ejection fraction >47% by radionucleotide angiogram or echocardiogram.
- •Adequate pulmonary function defined as:Uncorrected diffusing capacity of the lungs for carbon monoxide (DLCO) 50% by pulmonary function test.For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.
- •Eligibility for Moderate Intensity, Reduced Intensity Regimen and Fanconi's Anemia (Regimens C, D and E)
- •Adequate renal function defined as: Serum creatinine <2.0 x normal, or Creatinine clearance or radioisotope GFR 40 ml/min/m2 or >40 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
- •Adequate liver function defined as:Total bilirubin <2.5 x normal, or SGOT (AST) or SGPT (ALT) <5.0 x normal
- •Adequate cardiac function defined as:Shortening fraction of >25% by echocardiogram, or Ejection fraction >40% by radionucleotide angiogram or echocardiogram.
- •Adequate pulmonary function defined as:Uncorrected DLCO >35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.
排除标准
- •Females who are pregnant or breast-feeding
- •Patients with documented uncontrolled infection at the time of study entry
研究组 & 干预措施
A: Full Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF).
干预措施: Total Body Irradiation (Radiation)
A: Full Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF).
干预措施: Cyclophosphamide (Drug)
A: Full Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF).
干预措施: Rabbit Antithymocyte Globulin (Drug)
A: Full Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF).
干预措施: Thiotepa (Drug)
B: Full intensity without TBI
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with double cord blood infusion on Day 0. Granulocyte-macrophage colony-stimulating factor (GM-CSF) hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Melphalan (Drug)
B: Full intensity without TBI
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with double cord blood infusion on Day 0. Granulocyte-macrophage colony-stimulating factor (GM-CSF) hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Busulfan (Drug)
B: Full intensity without TBI
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with double cord blood infusion on Day 0. Granulocyte-macrophage colony-stimulating factor (GM-CSF) hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Rabbit Antithymocyte Globulin (Drug)
C: Moderate Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -8. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Alemtuzumab (Drug)
C: Moderate Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -8. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Busulfan (Drug)
C: Moderate Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -8. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Fludarabine (Drug)
D: Reduced Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -6. Patients will receive busulfan twice daily on Days -6, and-5; fludarabine on Days -6, -5, -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Busulfan (Drug)
D: Reduced Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -6. Patients will receive busulfan twice daily on Days -6, and-5; fludarabine on Days -6, -5, -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Fludarabine (Drug)
D: Reduced Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -6. Patients will receive busulfan twice daily on Days -6, and-5; fludarabine on Days -6, -5, -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Rabbit Antithymocyte Globulin (Drug)
E: Fanconi's Anemia
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Total Body Irradiation (Radiation)
E: Fanconi's Anemia
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Fludarabine (Drug)
E: Fanconi's Anemia
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Cyclophosphamide (Drug)
E: Fanconi's Anemia
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Horse Antithymocyte Globulin (Drug)
F: Regimen for non-malignant diseases
Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Busulfan (Drug)
F: Regimen for non-malignant diseases
Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Phenytoin (Drug)
F: Regimen for non-malignant diseases
Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Cyclophosphamide (Drug)
F: Regimen for non-malignant diseases
Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
干预措施: Rabbit Antithymocyte Globulin (Drug)
结局指标
主要结局
Graft Failure Rate
时间窗: Up to 2 years
Number of patients to experience graft failure.
Response Rate (Complete and Partial Response)
时间窗: Up to 2 years
Response rate to each regimen will be measured.
Overall Survival (OS)
时间窗: Up to 2 years
OS will be summarized using the Kaplan and Meier curves.
Disease Free Survival (DFS)
时间窗: Up to 2 years
DFS will be summarized using the Kaplan and Meier curves.
次要结局
未报告次要终点
研究者
Prakash Satwani
Associate Professor of Pediatrics at the Columbia University Med, Department of Pediatrics BMT
Columbia University