Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation
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.
|Study Design:||Allocation: Randomized
Primary Purpose: Supportive Care
|Official Title:||Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose|
- 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)
- Survival at 100 days following stem cell transplantation
- Toxicity by NCI Common Toxicity Criteria version 2.0 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
- Occurrence of other adverse events by NCI Common Toxicity Criteria version 2.0 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
- Feasibility of pharmacokinetics (PK) across dose arms and the PK of defibrotide by PK analysis
|Study Start Date:||March 1999|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003966
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Paul G.G. Richardson, MD||Dana-Farber Cancer Institute|