Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation
- Registration Number
- NCT00003966
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
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.
- Detailed Description
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.
PROJECTED ACCRUAL: A total of 140 patients (70 per treatment arm) will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 151
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Lower dose defibrotide 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 Arm B Higher Dose defibrotide 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
- Primary Outcome Measures
Name Time Method 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) 60 Days
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (9)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States