Efficacy Study of a TXA127 to Reduce Graft-vs-Host Disease in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
2016年8月29日 更新者：Tarix Pharmaceuticals
Phase II Evaluation of the Efficacy of TXA127 (Angiotensin 1-7) to Reduce Acute Graft-vs.-Host Disease in Adults Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
The purpose of this study is to evaluate the efficacy of TXA127 to reduce the incidence (Grade II-IV) of acute Graft-vs.-Host
Disease (aGVHD) in adult subjects undergoing allogeneic peripheral blood stem cell transplantation (PBSCT).
The study will also evaluate the effects of TXA127 on incidence, severity and duration of mucositis; neutrophil engraftment and platelet recovery; platelet transfusion requirements; immune reconstitution; and duration of corticosteroid use.
TXA127 has shown to be well tolerated by patients and appears to induce rapid production of neutrophils and platelets in the bloodstream, as well as increase the immune system components.
TXA127 has also been shown reduce the severity of chemotherapy-induced mucositis.
研究概览
详细说明
Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as an effective treatment for malignant disease.
The three most common sources for stem cells used in HSCT are bone marrow (BM), umbilical cord blood (UCB), and peripheral blood stem cells (PBSC).
In a retrospective review of 1,525 adults with acute leukemia receiving allogeneic transplants between 2002 and 2006, UCB accounted for 10.8%, PBSC for 58.2%, and BM for 31% of the population (Eapen et al., 2010).
PBSC as a source of hematopoietic stem cells for transplantation has advantages over bone marrow in terms of donation ease and comfort and over cord blood in terms of adequate cell dose.
However, PBSC transplantations are associated with an increased incidence of graft-versus-host disease (GVHD).
Based on current literature acute GVHD (aGVHD) is reported in 48-80% of PBSCT recipients (Eapen et al., 2010, Ferrara et al., 2009).
Additionally, the myeloablative conditioning regimens used for these transplants often result in mucositis which can be debilitating to patients.
TXA127 is pharmaceutically-formulated angiotensin 1-7, a non-hypertensive derivative of angiotensin II.
TXA127 has multilineage effects on hematopoietic progenitors in vitro and in vivo.
The hematopoietic properties demonstrated in preclinical and clinical studies support the investigation of TXA127 to reduce the incidence of aGVHD and mucositis in this patient population.
研究类型
介入性
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
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Georgia
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Atlanta、Georgia、美国、30322
- Winship Cancer Institute, Emory University
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Missouri
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St Louis、Missouri、美国、63110
- Siteman Cancer Center
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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 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Provided written informed consent.
- ≥18 years of age.
- Meet institutional standard criteria for PBSC transplantation
- Myeloablative conditioning regimen
- Histologically confirmed diagnosis of a hematologic malignancy.
- Life expectancy of >4 months.
- Female subjects capable of reproduction (defined as a subject who has started menses) must agree to the following: 1) Use of an effective oral or IM contraceptive method during the course of the study and 2 months following the last administration of Investigational Product; and 2) must have a negative pregnancy test result within 7 days prior to first Investigational Product dose.
Exclusion Criteria:
- Uncontrolled infection at the time of transplant.
- Pregnant or breastfeeding.
- Known to be seropositive for HIV or HTLV-1.
- Active CNS disease at the time of study enrollment.
- Treatment with an investigational agent within 30 days of anticipated administration of the first dose of Investigational Product.
- Current alcohol use, illicit drug use or any other condition (e.g., psychiatric disorder) that, in the opinion of the Investigator, may interfere with the subject's ability to comply with the study requirements or visit schedule.
- Any co-morbid condition which, in the view of the Principal Investigators, renders the subject at too high a risk from treatment complications and regimen-related morbidity/mortality.
- Prophylactic treatment with palifermin for mucositis.
- Subjects with a known sensitivity to any of the Investigational Product components.
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：支持治疗
- 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 |
|---|---|
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实验性的：TXA127, blood draws, physical exams
Single-arm safety/efficacy trial of TXA127 (Angiotensin 1-7) in subjects undergoing allogeneic peripheral blood stem cell transplantation for the treatment of a variety of hematologic malignancies for whom there is no available therapy with substantive anti-disease effect.
Treatment dose is 300 mcg/kg/day TXA127.
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注射剂，300mcg/kg/天，持续 28 天
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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 |
|---|---|---|
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II-IV 级急性移植物抗宿主病 (aGVHD) 的发生率
大体时间：移植后 100 天
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II-IV 级急性移植物抗宿主病 (aGVHD) 的发病率将使用 Przepiorka 等人定义的临床分期和分级标准进行评估。 (1995)。
还将评估 aGVHD 的持续时间和严重程度。
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移植后 100 天
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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血小板输注要求
大体时间：移植后 100 天
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血小板输注要求基于累积的血小板输注单位和累积的血小板输注天数。
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移植后 100 天
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免疫重建
大体时间：移植后 100 天
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将通过测量 CD3+、CD4+、CD8+、CD19+ 和 CD56+ 细胞的外周血浓度来评估免疫重建（在研究第 62 天和第 100 天进行）。
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移植后 100 天
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使用皮质类固醇的持续时间
大体时间：移植后 100 天
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皮质类固醇用于 GVHD 的持续时间将按频率（即天数）进行总结。
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移植后 100 天
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Incidence, duration, and severity grade of mucositis
大体时间：100 days post-transplantation
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Incidence of mucositis is defined by the occurrence of least one adverse event with MedDRA preferred term that includes "mucositis" or "stomatitis".
The severity grade will be determined by NCI-CTCAE.
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100 days post-transplantation
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Neutrophil engraftment and platelet recovery
大体时间：100 days post-transplantation
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Time to initial neutrophil engraftment is defined as the number of days from PBSC transplant to the first of 3 consecutive days of an ANC ≥0.5 × 10^9/L.
Time to initial platelet recovery is defined as the number of days from PBSC transplant to the first of 3 consecutive platelet count measurements tested on different days with a count ≥20 × 10^9/L with no platelet transfusion in the prior 7 days.
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100 days post-transplantation
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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：Edmund K Waller, MD,PhD,FACP、Emory University
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
2013年12月1日
初级完成 (实际的)
2013年12月1日
研究完成 (实际的)
2013年12月1日
研究注册日期
首次提交
2013年6月17日
首先提交符合 QC 标准的
2013年6月17日
首次发布 (估计)
2013年6月20日
研究记录更新
最后更新发布 (估计)
2016年8月31日
上次提交的符合 QC 标准的更新
2016年8月29日
最后验证
2016年8月1日
更多信息
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.
TXA127的临床试验
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Tarix Pharmaceuticals撤销
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Tarix PharmaceuticalsConstant Therapeutics LLC终止
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Sean CollinsNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)完全的
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US Biotest, Inc.Tarix Pharmaceuticals终止
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University of Southern CaliforniaCrowley Carter Foundation; Don and Linda Carter Foundation; United Cerebral Palsy Foundation完全的