Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 9
- 主要终点
- Complete Response Rate as measured by a total bilirubin of < 2 mg/dL and resolution of multi-organ failure attributable to veno-occlusive disease (VOD)
研究概览
简要总结
RATIONALE: Giving defibrotide may be an effective treatment for liver damage that may result following peripheral stem cell transplantation.
PURPOSE: This randomized phase II trial is studying defibrotide to see how well it works in treating patients with severe liver disease after undergoing peripheral stem cell transplantation.
详细描述
OBJECTIVES:
- Determine complete response rate in post-hematopoietic stem cell transplant patients with severe veno-occlusive disease of the liver treated with defibrotide.
- Determine the minimal effective dose of this drug in these patients.
- Assess toxicity and adverse side effects of this drug in these patients.
OUTLINE: This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide.
- Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours.
- Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours.
In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A Lower dose
This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide.
- Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours.
In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
干预措施: defibrotide (Drug)
Arm B Higher Dose
This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide.
- Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours.
In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
干预措施: defibrotide (Drug)
结局指标
主要结局
Complete Response Rate as measured by a total bilirubin of < 2 mg/dL and resolution of multi-organ failure attributable to veno-occlusive disease (VOD)
时间窗: 60 Days
次要结局
- Survival at 100 days following stem cell transplantation(100 days following stem cell transplantation)
- Toxicity by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion(during study and 30 Days after study completion)
- Grade 3-4 end organ dysfunction attributable to defibrotide as determined by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion(during study and 30 Days after study completion)
- Occurrence of other adverse events by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion(during study and 30 Days after study completion)
- Effect of drug on plasminogen activator inhibitor-1 (PAI-1) determination of dose-relationship between drug and/or VOD response as measured by survival, PAI-1 levels, and research assays at day 100(100 Days)
- Feasibility of pharmacokinetics (PK) across dose arms and the PK of defibrotide by PK analysis
研究者
Paul G. Richardson, MD
Richardson, Paul MD
Dana-Farber Cancer Institute