Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies
RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and 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 chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.
研究概览
地位
详细说明
OBJECTIVES:
Primary
- Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100.
Secondary
- Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
- Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
- Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
- Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.
OUTLINE: This is a pilot study.
- Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
- Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
California
-
San Francisco、California、美国、94143-0324
- UCSF Comprehensive Cancer Center
-
-
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 1 of the following advanced hematologic malignancies:
Acute myeloid leukemia (AML) meeting the following criteria:
- Considered incurable with chemotherapy
- Marrow blasts ≤ 10% (may be achieved using standard chemotherapy regimen)
Meets any of the following criteria:
- High-risk cytogenetics (-7, -7q, -5, -5q, t(6,9), t(9,11), complex [≥ 3 abnormalities], Philadelphia chromosome positive [Ph+])
- AML evolved from prior myelodysplasia
- AML secondary to prior chemotherapy
- Failed to achieve remission
- In second or subsequent remission
- Refractory relapse
Myelodysplastic syndromes (MDS) meeting the following criteria:
Must have high-risk features, including any of the following:
- Intermediate-2 or high risk International Prognostic Scoring System (IPSS) score
- Chronic myelomonocytic leukemia
- Marrow blasts ≤ 20% (chemotherapy may be given to achieve target blast levels)
- No rapidly progressive disease
Acute lymphoblastic leukemia meeting the following criteria:
- Considered incurable with chemotherapy
Meets any of the following criteria:
- High-risk cytogenetics (Ph+, t(4,11), 11q23 abnormalities, or monosomy 7)
- Required > 1 induction course to achieve remission
- Failed to enter remission
- In second or subsequent remission
- Marrow blasts ≤ 10% (chemotherapy may be given to achieve target blast levels)
Chronic myelogenous leukemia (CML) meeting 1 of the following criteria:
- Chronic phase CML that failed imatinib mesylate therapy, as defined by progressive disease or failed to achieve a major cytogenetic response at 1 year after initiation of therapy
Accelerated phase CML meeting 1 of the following criteria:
- Failed to achieve a complete cytogenetic remission at 1 year after initiation of therapy
- Failed to achieve any cytogenetic response after 6 months of therapy
- Progressive disease, as demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks
- In blast crisis with < 10% blasts in bone marrow
Multiple myeloma meeting the following criteria:
- Stage I-III disease
Meets any of the following criteria:
- In relapse after autologous transplantation
- Refractory to ≥ 2 prior conventional myeloma therapies
- Chromosome 13 abnormalities (may be enrolled at diagnosis or after initial progression)
Lymphoma
The following subtypes are eligible:
- Diffuse large cell
- Follicular large cell
- Mantle cell
- Peripheral T-cell
- T-natural killer (T-NK) cell
- Hodgkin's lymphoma
- Must have progressed, recurred after prior therapy, or failed to respond to primary therapy
- Relapsed disease after autologous stem cell transplantation (SCT) allowed
Low-grade non-Hodgkin's lymphoma meeting 1 of the following criteria:
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
Chronic lymphocytic leukemia
- Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
- Relapsed after autologous SCT
Meets 1 of the following criteria:
- Age 55-70 years
Under age 55 and deemed ineligible for conventional high-dose chemotherapy, as indicated by any of the following:
- Poor cardiac function (i.e., LVEF < 40%)
- Poor pulmonary function (i.e., DLCO < 50%)
- Hepatic dysfunction
- Prior myeloablative therapy
- Not eligible for autologous SCT or conventional therapy
Umbilical cord blood donor available
- Matched at ≥ 4 of 6 HLA antigens (A, B, and DR)
- Has 1-3 units of umbilical cord blood available
- Must not have an HLA-identical or 1 antigen mismatched related donor or potential HLA-matched unrelated donor readily available NOTE: A new classification scheme for adult non-Hodgkin's 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.
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Creatinine clearance > 40 mL/min
- Creatinine < 2.0 mg/dL
- AST and alkaline phosphatase < 3 times upper limit of normal (ULN)
- Bilirubin < 2.0 mg/dL
Hepatitis C or active hepatitis B virus (HBV) allowed if ≤ grade 2 fibrosis and/or inflammation by liver biopsy
- Patients with history of HBV infection should be tested for hepatitis B epsilon (HBe) antigen, anti-HBe, and HBV DNA (quantitative)
- Patients with active HBV viral replication should receive antiviral therapy
- Ejection fraction > 30%
- DLCO ≥ 40%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring ongoing antibiotic treatment
- HIV negative
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
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)
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 |
---|---|---|
Safety and Feasibility of donor cord blood transplant
大体时间:up to 36 months post transplant
|
as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
|
up to 36 months post transplant
|
合作者和调查者
调查人员
- 首席研究员:Thomas G. Martin, MD、University of California, San Francisco
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 (实际的)
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
- 母细胞期慢性粒细胞白血病
- 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
- IV 期 1 级滤泡性淋巴瘤
- IV 期 2 级滤泡性淋巴瘤
- III期套细胞淋巴瘤
- IV期套细胞淋巴瘤
- II期多发性骨髓瘤
- III期多发性骨髓瘤
- 复发性 1 级滤泡性淋巴瘤
- 复发性 2 级滤泡性淋巴瘤
- 复发性边缘区淋巴瘤
- 复发性小淋巴细胞淋巴瘤
- III期小淋巴细胞淋巴瘤
- III期边缘区淋巴瘤
- IV期小淋巴细胞淋巴瘤
- IV期边缘区淋巴瘤
- 黏膜相关淋巴组织结外边缘区B细胞淋巴瘤
- 淋巴结边缘区B细胞淋巴瘤
- 脾边缘区淋巴瘤
- I期多发性骨髓瘤
- 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
- 复发性皮肤 T 细胞非霍奇金淋巴瘤
- III期成人T细胞白血病/淋巴瘤
- IV 期成人 T 细胞白血病/淋巴瘤
- 复发性成人 T 细胞白血病/淋巴瘤
- 血管免疫母细胞性T细胞淋巴瘤
- 间变性大细胞淋巴瘤
- 复发性蕈样肉芽肿/Sezary 综合征
- 难治性多发性骨髓瘤
- 复发性成人急性淋巴细胞白血病
- 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
- CDR0000465362
- UCSF-04253
- UCSF-2407
- UCSF-H24045-25271-02
药物和器械信息、研究文件
研究美国 FDA 监管的药品
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
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
抗胸腺细胞球蛋白的临床试验
-
Hanyang University Seoul HospitalSeegene Medical Foundation完全的
-
Radboud University Medical CenterLeiden University Medical Center尚未招聘
-
University of Georgia招聘中消息曝光(顺序:Regular Then Flavor) | 消息曝光(顺序:Flavor Then Regular) | 无消息暴露(控制条件)美国