Allogeneic Hematopoietic Stem Cell Transplant for Patients With Immunologic or Histiocytic Disorders Using a Non-Myeloablative Preparative Regimen to Achieve Stable Mixed Chimerism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of Subjects With Mixed Chimerism
研究概览
简要总结
This study tests the clinical outcomes of a preparative regimen of fludarabine (FLU), anti-thymocyte globulin (ATG)/or Campath, and melphalan; followed by hematopoietic stem cell transplant, and a post transplant regimen of Cyclosporin A (CsA) in patients with immunologic or histiocytic disorders. The researchers hypothesize that this regimen will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease (GVHD).
Patients will be randomized biologically into one of 3 arms based upon donor availability: (a) human leukocyte antigen (HLA) genotypic matched sibling donor, (b) HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, (c) two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).
详细描述
Prior to transplantation, subjects will receive Melphalan, Fludarabine and Anti-Thymocyte Globulin (ATG) or Campath. These three drugs are being given to subjects to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.
After stem cell transplantation, subjects will be given Cyclosporin A (CsA) and mycophenolate mofetil (MMF) to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.
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
- — 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with immunodeficiencies or histiocytic disorders 0-35 years of age with an acceptable stem cell donor and disease characteristic defined by the following:
- •Patients with histocytic disorders (hemophagocytic lymphohistiocytosis of any etiology and refractory Langerhans cell histiocytosis) who do not meet eligibility criteria for a myeloablative transplant procedure
- •Patients with immunodeficiency disorders in whom residual immune function may not require a fully myeloablative preparative regimen or patient is ineligible for standard myeloablative preparative regimen (any form of severe combined immunodeficiency [SCID], or other immunodeficiency with T cell defect)
- •Patients with immunodeficiency disorders that have had poor outcome with myeloablative stem cell transplants (including, but not limited to, common variable immunodeficiency [CVID], Wiskott Aldrich Syndrome [WAS] if > 5 years of age, ataxia telangiectasia)
- •Patients with immunodeficiencies or histocytic disorders that require a second stem cell transplant (SCT) for any reason
排除标准
- •Karnofsky or Lansky performance score <70
- •Glomerular filtration rate (GFR)<30% predicted
- •Cardiac function <50% normal by echocardiogram
- •Serum creatinine > 2x normal for age/weight
- •Pregnant or lactating females
- •Active serious infection that has not had an adequate course of therapy pre-SCT. Any patient with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) or human immunodeficiency virus (HIV) seropositivity
研究组 & 干预措施
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Stem Cell Transplant (Procedure)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Fludarabine (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Melphalan (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Anti-thymocyte globulin (ATG) (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Campath 1H (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Cyclosporin A (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Mycophenolate mofetil (Drug)
Arm 1 - Matched sibling donor
Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Intravenous immunoglobulin (IVIG) (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Stem Cell Transplant (Procedure)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Fludarabine (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Melphalan (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Anti-thymocyte globulin (ATG) (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Campath 1H (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Cyclosporin A (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Mycophenolate mofetil (Drug)
Arm 2 - Matched unrelated donor
Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Intravenous immunoglobulin (IVIG) (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Stem Cell Transplant (Procedure)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Fludarabine (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Melphalan (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Anti-thymocyte globulin (ATG) (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Campath 1H (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Cyclosporin A (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Mycophenolate mofetil (Drug)
Arm 3 - Mismatched double cord donors
Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
干预措施: Intravenous immunoglobulin (IVIG) (Drug)
结局指标
主要结局
Number of Subjects With Mixed Chimerism
时间窗: Day 100
\>10% Donor Cells at Day 100
次要结局
- Number of Subjects Alive at 100 Days(Day 100)
- Number of Subjects Alive at One Year(Day 365)
- Compare Quality of Life (QOL)(Pretransplant, 1 year, 2 years and 5 years)
- Incidence of Chronic Graft Versus Host Disease (cGVHD)(6 months and 1 year)
- Percentage of Donor Chimerism at 100 Days(Day 100)
- Percentage of Donor Chimerism at 180 Days(Day 180)
- Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD)(Day 100)
- Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD)(Day 100)
- Percentage of Donor Chimerism at 365 Days(Day 365)