The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-versus-Host Prophylaxis With Tacrolimus and Mycophenolate Mofetil
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Number of Participants With 100-day Non-relapse Mortality
研究概览
简要总结
RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before and after transplant may stop this from happening.
PURPOSE: To look at the ability of umbilical cord blood cells from one or two unrelated donors to serve as a source of stem cells for people needing a bone marrow transplant.
详细描述
OBJECTIVES:
Primary
- To determine the safety (as assessed by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord stem cell transplantation in patients with hematological malignancies receiving graft-versus-host disease (GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).
Secondary
- To assess sustained donor engraftment, neutrophil recovery, platelet recovery, incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD, relapse rate, 100-day all-cause mortality, overall survival, and immune reconstitution after single or double umbilical cord stem cell transplantation in patients with hematologic malignancies receiving graft-versus-host disease(GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).
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 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General (Adults and Pediatrics)
- •Only one of the following should be present:
- •Acute leukemia (lymphocytic or myeloid or undifferentiated or biphenotypic) in complete remission 2 or beyond
- •Acute lymphocytic leukemia, Philadelphia chromosome positive in complete remission 1 or beyond
- •Acute myeloid leukemia in complete remission 1 if it has evolved from a myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS).
- •Acute leukemia in complete remission 1 if there is a failure to recover normal blood counts or the development of MDS following induction chemotherapy.
- •Therapy related acute leukemia in complete remission 1 or beyond
- •Chronic myeloid leukemia (CML) chronic phase-1 (imatinib failures, imatinib intolerance), or any CML beyond first chronic phase
- •Myelodysplastic syndromes (Intermediate -1 or higher risk by IPSS)
- •Therapy related MDS (irrespective of IPSS)
- •Multiple myeloma must have had prior chemotherapy or autologous transplant
- •Chronic lymphocytic leukemia must have failed two lines of conventional therapy but still chemosensitive to third line therapy.
- •Chemosensitive Non-Hodgkin's lymphoma or Hodgkin's lymphoma in CR or PR after failing induction therapy.
- •High risk acute leukemia/lymphoma eg Nk/T cell, HTLV associated leukemia/lymphoma, other T cell lymphoma/leukemia in first best response
- •For patients with acute leukemia-they must be in a remission (less than 5% leukemic marrow blasts) at time of study entry.
- •Inclusion Criteria (Adults - 18 years or older)
- •Karnofsky score of > 70%
- •Estimated creatinine clearance of > 60 ml/min
- •Left ventricular ejection fraction of >50%
- •Pulmonary function test with DLCO, FEV1 and FVC of >60%
- •Total bilirubin and SGOT of < 3.0 x upper limits of normal
- •Note: Age 18- 40 years for adult myeloablative conditioning Age > 40 -50 years for adult reduced intensity conditioning
- •Inclusion Criteria (Pediatrics - 18 years and younger)
- •Karnofsky or Lansky score of > 70%
- •Estimated Creatinine clearance of > 60 ml/min
- •Left ventricular ejection fraction of >50%
- •Pulmonary function test with FEV1 and FVC of >60% (for patients >6 years of age)
- •Total bilirubin and SGOT of < 3.0 x upper limits of normal
- •Note: All pediatric patients will receive myeloablative conditioning
- •Inclusion Criteria - Donor Issues
- •No available HLA identical or 1 antigen/allele mismatched (Class I-A, B or Class II DR locus) related donor
- •Inclusion Criteria: Umbilical Cord Blood Unit-HLA Typing
- •At least a HLA 4/6 match (Class I-A, B by low resolution, Class II-DR by high resolution) to recipient
- •For double UCB SCT each unit should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to recipient, and should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to each other
- •Inclusion Criteria: Umbilical Cord Blood Unit-Cell dose
- •For Single UCB SCT: the unit will have ≥ 3.5 X 107 NC/kg of recipient body weight (For pediatric patients a cell dose ≥ 3.0 X 107 NC/kg of recipient body weight is acceptable). Recipient body weight will be determined as per standard guidelines.
- •For Double UCB SCT: (done only if no single UCB unit ≥ 3.5 X 107 NC/kg of recipient body weight is available for adults, and ≥ 3.0 X 107 NC/kg of recipient body weight is available for pediatric patients )
- •The larger of the two units (UCB1) will have a minimum cell dose of 2.0 X 107 NC/kg of recipient body weight. The smaller of the two units (UCB2) will have a minimum of 0.5 X 107 NC/kg of recipient body weight.
- •The total cell dose UCB1 + UCB2 will be ≥ 2.5 X 107 NC/kg of recipient body weight.
- •Adult patients eligible for a double UCB SCT but without an appropriate second UCB unit will be enrolled in the study if their single UCB unit contains ≥ 2.5 x 107 NC/kg recipient body weight.
- •Exclusion Criteria
- •Organ dysfunction as per standard guidelines. Unable to give informed consent (for adults only)
- •Pregnant or lactating
- •Sexually active individuals capable of becoming pregnant or causing a pregnancy who are unable or unwilling to use appropriate contraceptives.
- •Active use of illicit drugs as evidenced by a positive toxicology screen for a substance not prescribed by a medical professional just prior to initiating the preparative regimen
- •Actively smoking as evidenced by a positive nicotine screen just prior to initiating the preparative regimen
- •HIV positive
- •Patients with other unrelated malignancies will be excluded except:
- •diagnosis of skin cancer (squamous cell or basal cell)
- •diagnosis of cervical dysplasia (CIN I-III)
- 另有 2 项未显示
排除标准
- 未提供
研究组 & 干预措施
Reduced-intensity conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
干预措施: total-body irradiation (Radiation)
Pediatric Myeloablative conditioning
Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
干预措施: anti-thymocyte globulin (Biological)
Pediatric Myeloablative conditioning
Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
干预措施: cyclophosphamide (Drug)
Pediatric Myeloablative conditioning
Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
干预措施: methylprednisolone (Drug)
Pediatric Myeloablative conditioning
Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
干预措施: total-body irradiation (Radiation)
Adult Myeloablative conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
干预措施: cyclophosphamide (Drug)
Adult Myeloablative conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
干预措施: fludarabine phosphate (Drug)
Adult Myeloablative conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
干预措施: total-body irradiation (Radiation)
Reduced-intensity conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
干预措施: cyclophosphamide (Drug)
Reduced-intensity conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
干预措施: fludarabine phosphate (Drug)
结局指标
主要结局
Number of Participants With 100-day Non-relapse Mortality
时间窗: 100 days
Evaluate the safety (as determined by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord blood (UCB)stem cell transplant (SCT) in adult or pediatric patients with hematologic malignancies receiving graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
次要结局
- Number of Participants With Sustained Donor Engraftment of Umbilical Cord Blood Stem Cells(42 days)
- Number of Participants Who Relapsed at 1 Year(1 year)
- Number of Participants With Acute Graft-versus-host Disease (GVHD)(100 days)
- Number of Subjects With All-cause Mortality(at 100 days)
- Overall Survival(1 year)
- Number of Participants With Chronic Graft Versus Host Disease (GVHD)(100 days)
研究者
Brian Engelhardt, MD
Assistant Professor of Medicine; Hematologist/Oncologist
Vanderbilt-Ingram Cancer Center