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Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer

2013年10月28日 更新者:Northside Hospital, Inc.

A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer 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 high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.

研究概览

详细说明

OBJECTIVES:

Primary

  • To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies.

Secondary

  • To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients.
  • To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT.
  • To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0.
  • Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease.

After completion of PBSCT, patients are followed periodically for 1 year.

研究类型

介入性

注册 (实际的)

20

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Georgia
      • Atlanta、Georgia、美国、30342
        • Blood and Marrow Transplant Group of Georgia

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 60年 (成人)

接受健康志愿者

有资格学习的性别

全部

描述

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following high-risk hematologic malignancies:

    • Chronic myelogenous leukemia meeting one of the following criteria:

      • Disease in chronic phase and resistant to available tyrosine kinase inhibitors
      • Disease in accelerated phase
      • Disease with blast crisis that has entered into a second chronic phase after induction chemotherapy
    • Acute myelogenous leukemia meeting the following criteria:

      • Marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
      • Must meet one of the following criteria:

        • Disease in second or subsequent complete remission
        • Primary induction chemotherapy failure with disease subsequently entering complete remission
        • Disease in first complete remission with poor-risk cytogenetics or arising from preceding hematological disease
    • Myelodysplastic syndrome meeting at least one of the following criteria:

      • Treatment-related
      • Monosomy 7 or complex cytogenetics
      • International prognostic scoring system score ≥ 1.5
      • Chronic myelomonocytic leukemia
    • Acute lymphocytic leukemia or lymphoblastic lymphoma meeting the following criteria:

      • Marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
      • Must meet one of the following criteria:

        • Disease in second or subsequent complete remission
        • Acute lymphocytic leukemia with poor-risk karyotype [e.g., t(9;22) or bcr-abl fusion, t(4;11), or other MLL translocation] and in first complete remission
    • Chronic lymphocytic leukemia or prolymphocytic leukemia meeting both of the following criteria:

      • Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
      • In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
    • Hodgkin or non-Hodgkin lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse disease) meeting the following criteria:

      • Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
      • In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
  • No available matched related or unrelated donor OR a matched related or unrelated donor will not be available in the time frame necessary to perform a transplant
  • Availability of a first-degree relative (parent, child, sibling) matched at 3/6-5/6 loci (HLA-A, -B, -DR)

    • Donor must be willing to donate mobilized peripheral blood stem cells
    • No positive HLA crossmatch in the host-vs-graft direction or high titer donor-specific antibodies

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Bilirubin < 2 mg/dL (unless due to hemolysis, Gilbert syndrome, or primary malignancy)
  • Creatinine < 2 mg/dL OR creatinine clearance ≥ 40 mL/min
  • Not pregnant
  • Fertile patients must use effective contraception
  • LVEF (Left ventriculr ejection fraction) ≥ 45%
  • FEV_1 and forced vital capacity ≥ 50% predicted
  • No HIV positivity
  • No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment and follow-up

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No immunosuppressive agents ≤ 24 hours after completion of post-transplant cyclophosphamide (including steroids as antiemetics)

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Myeloablative Haploidentical Transplant
All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.
110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)
14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).
30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)
15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.
其他名称:
  • 细胞概念
0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.
其他名称:
  • Prograf, FK-506
Patients to received unmanipulated PBSCs on Day 0
其他名称:
  • Allo HSCT
patients to receive unmanipulated PBSCs on day 0
其他名称:
  • allogeneic hematopoietic stem cell transplant

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Incidence of Graft Rejection for Patients at Day 100
大体时间:Day 100
Number of patients who experienced graft rejection by Day 100
Day 100
Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)
大体时间:Day 100
Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence
Day 100

次要结果测量

结果测量
措施说明
大体时间
Overall Survival at Day 100
大体时间:Day 100
Overall survival is assessed, without regard to disease status, post-transplant, at Day 100.
Day 100
Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)
大体时间:1 year
Non-relapse mortality refers to whether a patient dies of causes related to something other than the primary disease.
1 year
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation
大体时间:Day 30
Chimerism analysis of peripheral blood mononuclear cells using PCR (polymerase chain reaction) for STR/VNTR (short tandme repeat/variable number tandem repeat) will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Day 30
Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)
大体时间:Day 100
Day 100
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation
大体时间:Day 60
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Day 60
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation
大体时间:Day 90
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Day 90
Overall Survival at 12 Months
大体时间:12 months
Overall survival, defined as a patient being alive after transplant, is without regard to disease status.
12 months
Disease Free Survival at 12 Months
大体时间:12 months
Disease free survival refers to patients with no evidence of disease after transplant, at the 12 month time point.
12 months
Disease Free Survival at Day 100
大体时间:Day 100
Disease free survival refers to patients with no evidence of disease after transplant, at the Day 100 time point.
Day 100

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Scott R. Solomon, MD、Blood and Marrow Transplant Group of Georgia
  • 首席研究员:H. Kent Holland, MD、Blood and Marrow Transplant Group of Georgia
  • 首席研究员:Lawrence E. Morris, MD、Blood and Marrow Transplant Group of Georgia

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2008年10月1日

初级完成 (实际的)

2011年4月1日

研究完成 (实际的)

2012年4月1日

研究注册日期

首次提交

2008年10月29日

首先提交符合 QC 标准的

2008年10月29日

首次发布 (估计)

2008年10月31日

研究记录更新

最后更新发布 (估计)

2013年11月21日

上次提交的符合 QC 标准的更新

2013年10月28日

最后验证

2013年3月1日

更多信息

与本研究相关的术语

关键字

其他研究编号

  • CDR0000617648
  • BMTGG-NSH-864

药物和器械信息、研究文件

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研究美国 FDA 监管的设备产品

在美国制造并从美国出口的产品

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