Randomized Trial of Unmanipulated Versus Expanded Cord Blood
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Time To Neutrophil Engraftment
研究概览
简要总结
The goal of this clinical research study is to learn if combining cord blood units to make the cells "take" faster in recipients will help to improve the results of cord blood transplants.
详细描述
Cord blood is a source of blood forming cells that can be used for transplantation. The major problem with this type of transplant is the small number of blood forming cells available in each cord unit, which may delay the "take" of the graft in the recipient. Two strategies may be used to try to overcome this problem. One method is the combination of 2 units of cord blood and the other is the growing of the cord blood cells in the laboratory before they are transplanted in order to increase their number.
Participants will be randomly assigned (as in the toss of a coin) to one of two groups. If you are assigned to Study Arm 1, you will receive two cord blood units combined without growing the cells in the laboratory. If you are assigned to Study Arm 2, you will receive one cord blood unit combined with one cord blood unit which will be grown in the laboratory for two weeks before you receive it. Neither you nor your doctors will know in advance to which arm you will be assigned.
Placement of central venous catheter for collection of "back-up" stem cells:
Before you have back-up stem cell collected or you receive chemotherapy, you will require placement of a hollow plastic tube (catheter) into a large vein inside your body. This catheter will be used to draw blood and to give medications and fluids. The catheter is inserted through the skin in the upper chest and extends into the right side of your heart. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.
Collection of back up stem cells:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease-Specific Eligibility Requirements: Patients must have one of the following hematologic malignancies:
- •Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS)
- •Acute Lymphoblastic Leukemia (ALL)
- •Chronic Myelogenous Leukemia (CML)
- •Non-Hodgkin's Lymphoma (NHL)
- •Hodgkin's Disease (HD)
- •Chronic Lymphocytic Leukemia (CLL)
- •Chronic eosinophilic leukemia or Philadelphia chromosome negative CML.
- •Greater than 1 month old and <=60 years old for full myeloablative therapy.
- •Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1E7 total nucleated cells/Kg recipient body weight in the pre-thawed fraction.
- •Patient must be willing to undergo bone marrow harvest or peripheral blood progenitor cell (PBPC) collection for use in case of engraftment failure. If the patient is unable or fails to successfully undergo the collection, a family member must be identified to donate hematopoietic stem cells for haploidentical transplant in case of engraftment failure. If autologous hematopoietic stem cells cannot be procured due to marrow contamination by malignancy, or due to harvest failure, and a haploidentical relative is not available or not willing to donate, two cord blood units can be used as the back-up graft.
- •Continuation to Criteria # 4: These units will be identified prior to enrollment in this study.
- •Regimen 1 (Myeloablative mel/thiotepa/fludarabine): 1.Patients with ALL, HD, NHL, AML, MDS, CML, CLL and Chronic eosinophilic leukemia who are candidates for full myeloablative therapy. 2.Performance score of at least 60% by Karnofsky (age >= 12 years), or Lansky Play-Performance Scale (age <12 years). 3.Age >=1 month <=60 years (high-dose).
- •Continuation to Criteria # 6: 4.Adequate major organ system function as demonstrated by:a. Left ventricular ejection function of at least 40%. b.Pulmonary function test demonstrating a diffusion capacity of at least 50%. predicted (high-dose). c.Creatinine < 1.6 mg/dL. d.serum glutamate pyruvate transaminase (SGPT)/bilirubin <= to 2.0 x normal (high-dose).
- •Eligibility for Regimen 2 (Non-myeloablative Cy-Flu-TBI):
- •Patients with ALL, AML, MDS, CML, NHL, CLL, Chronic eosinophilic leukemia and HD who are not candidates for full myeloablative therapy. All patients who received a prior autologous transplant are eligible.
- •Performance score of at least 60% by Karnofsky or PS < 3 (ECOG) (age >= 12 years), or Lansky Play-Performance Scale (age <12 years)
- •Age >= 1 month <=80 years
- •Continuation to Criteria # 8:
- •Left ventricular ejection function of at least 30%;
- •Pulmonary function test demonstrating a diffusion capacity of at least 40% predicted;
- •Creatinine < 3.0 mg/dL;
- •SGPT <= to 4.0 x normal.
- •Regimen 3 (Myeloablative VP16-TBI):
- •Patients with ALL who are candidates for myeloablative therapy, and require a TBI-containing regimen.
- •Performance score of at least 60% by Karnofsky or PS < 2 (ECOG) (age >= 12 years), or Lansky Play-Performance Scale (age <12 years).
- •Age >= 1 month <=50 years.
- •Organ function requirements: a. Left ventricular ejection function of at least 50%. b. Pulmonary function test demonstrating a diffusion capacity of at least 50% predicted. c. Creatinine < 1.6 mg/dL. d. SGPT <= 2.0 x normal.
排除标准
- •HIV positive.
- •Serious medical Condition.
- •Patients with signs & symptoms leading to positive lumbar puncture (malignant cells in the CSF) or to documented metastatic parenchymal disease are ineligible for this study.
- •Availability of appropriate, willing, HLA-matched related donor.
研究组 & 干预措施
Double Cord Blood Transplant Group
Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.
干预措施: Expanded allogeneic cord blood (CB) (Procedure)
Double Cord Blood Transplant Group
Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.
干预措施: Rituxan (Drug)
Double Cord Blood Transplant Group
Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.
干预措施: Melphalan (Drug)
Double Cord Blood Transplant Group
Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.
干预措施: Thiotepa (Drug)
Double Cord Blood Transplant Group
Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.
干预措施: Fludarabine (Drug)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: One Unmanipulated and One Expanded Cord Blood Unit (Procedure)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: Rituxan (Drug)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: Fludarabine (Drug)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: Cyclophosphamide (Drug)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: Mesna (Drug)
One Expanded Cord Blood Transplant Group
One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.
干预措施: Total body irradiation (TBI) (Radiation)
结局指标
主要结局
Time To Neutrophil Engraftment
时间窗: First 100 days, evaluation and blood tests twice weekly
Engraftment is defined as a sustained ANC \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment date is the first of the 3 days with sustained absolute neutrophil count (ANC) \>/= 0.5 x 10\^9/L.
Number of Participants With Engraftment
时间窗: First 100 days, evaluation and blood tests twice weekly
Engraftment defined as a sustained absolute neutrophil count (ANC) \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment Failure defined as ANC \<500/ul by day +42 and participant has no evidence of donor chimerism on bone marrow examination.
次要结局
- Rate of Acute Graft Versus Host Disease (GVHD)(Review over first 100 days)
- Rate of Chronic GVHD(Up to one year)
- Number of Participants Severity of Acute GVHD by Treatment Arm(Following first 100 days, up to one year)