Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer
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
地位
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
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
-
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Georgia
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Atlanta、Georgia、美国、30342
- Blood and Marrow Transplant Group of Georgia
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
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
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:
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:
Patients to received unmanipulated PBSCs on Day 0
其他名称:
patients to receive unmanipulated PBSCs on day 0
其他名称:
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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
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Number of patients who experienced graft rejection by Day 100
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Day 100
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Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)
大体时间:Day 100
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Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence
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Day 100
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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
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Overall survival is assessed, without regard to disease status, post-transplant, at Day 100.
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Day 100
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Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)
大体时间:1 year
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Non-relapse mortality refers to whether a patient dies of causes related to something other than the primary disease.
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1 year
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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
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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.
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Day 30
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Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)
大体时间:Day 100
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Day 100
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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
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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.
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Day 60
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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
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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.
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Day 90
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Overall Survival at 12 Months
大体时间:12 months
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Overall survival, defined as a patient being alive after transplant, is without regard to disease status.
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12 months
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Disease Free Survival at 12 Months
大体时间:12 months
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Disease free survival refers to patients with no evidence of disease after transplant, at the 12 month time point.
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12 months
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Disease Free Survival at Day 100
大体时间:Day 100
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Disease free survival refers to patients with no evidence of disease after transplant, at the Day 100 time point.
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Day 100
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合作者和调查者
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
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
- III期成人弥漫性大细胞淋巴瘤
- IV期3级滤泡性淋巴瘤
- IV期成人弥漫性大细胞淋巴瘤
- 复发性 3 级滤泡性淋巴瘤
- 复发性成人弥漫性大细胞淋巴瘤
- 慢性粒单核细胞白血病
- 新生骨髓增生异常综合征
- 既往治疗过的骨髓增生异常综合征
- 继发性骨髓增生异常综合征
- 具有 11q23 (MLL) 异常的成人急性髓性白血病
- 伴有 inv(16)(p13;q22) 的成人急性髓性白血病
- 成人急性髓性白血病伴 t(15;17)(q22;q12)
- 成人急性髓性白血病伴 t(16;16)(p13;q22)
- 成人急性髓性白血病伴 t(8;21)(q22;q22)
- 继发性急性髓性白血病
- 慢性期慢性粒细胞白血病
- 复发性成人急性髓性白血病
- 缓解期成人急性髓性白血病
- 复发性成人霍奇金淋巴瘤
- 复发性成人弥漫性小裂细胞淋巴瘤
- 复发性成人弥漫性混合细胞淋巴瘤
- 复发性慢性粒细胞白血病
- III 期 1 级滤泡性淋巴瘤
- III期2级滤泡性淋巴瘤
- III期3级滤泡性淋巴瘤
- III期成人弥漫性小裂细胞淋巴瘤
- III期成人弥漫性混合细胞淋巴瘤
- IV 期 1 级滤泡性淋巴瘤
- IV 期 2 级滤泡性淋巴瘤
- IV期成人弥漫性小裂细胞淋巴瘤
- IV期成人弥漫性混合细胞淋巴瘤
- III期套细胞淋巴瘤
- IV期套细胞淋巴瘤
- 复发性 1 级滤泡性淋巴瘤
- 复发性 2 级滤泡性淋巴瘤
- 非连续性 II 期 1 级滤泡性淋巴瘤
- 非连续性 II 期 2 级滤泡性淋巴瘤
- 非连续性 II 期成人弥漫性小裂细胞淋巴瘤
- 复发性套细胞淋巴瘤
- 难治性慢性淋巴细胞白血病
- III期慢性淋巴细胞白血病
- IV期慢性淋巴细胞白血病
- III期成人霍奇金淋巴瘤
- IV期成人霍奇金淋巴瘤
- III期成人淋巴母细胞淋巴瘤
- IV期成人淋巴母细胞淋巴瘤
- 幼淋巴细胞白血病
- 非连续性 II 期套细胞淋巴瘤
- 非连续性 II 期成人弥漫性大细胞淋巴瘤
- 非连续性 II 期成人弥漫性混合细胞淋巴瘤
- 非连续性 II 期成人淋巴母细胞淋巴瘤
- 非连续性 II 期 3 级滤泡性淋巴瘤
- 加速期慢性粒细胞白血病
- 缓解期成人急性淋巴细胞白血病
其他相关的 MeSH 术语
其他研究编号
- CDR0000617648
- BMTGG-NSH-864
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