Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients
The purpose of this study is to (1) demonstrate the efficacy and safety (toxicity) of 25 mg/kg/day of Defibrotide in patients with severe veno-occlusive disease (sVOD) and (2) evaluate serum and endothelial markers of VOD through the analysis of blood samples.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients: A Historically-Controlled, Multi-Center Phase 3 Study to Determine Safety & Efficacy|
- Complete Response at D+100 post stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ] [ Designated as safety issue: No ]
- Survival at D+100 following stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ] [ Designated as safety issue: No ]
- Long-term (6 month) survival rate [ Time Frame: 180 days post stem cell transplant ] [ Designated as safety issue: No ]
- Safety of the selected dose and schedule [ Time Frame: through 30 days from the last dose of Defibrotide ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2006|
|Study Completion Date:||November 2008|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
Defibrotide 6.25 mg/kg i.v. administered four times a day via 2 hour continuous infusion. Minimum duration 21 days.
This is a historically-controlled, multicenter, open label Phase 3 study to determine the safety and efficacy of 25 mg/kg/day of Defibrotide (DF) for the treatment of severe VOD in hematopoietic SCT patients.
In this study, the term "severe VOD" is defined as those patients who meet the Baltimore diagnostic criteria for VOD (total bilirubin >/= 2.0 mg/dL plus two of the following: ascites, >/=5% weight gain and hepatomegaly), who also have MOF (i.e., pulmonary and/or renal dysfunction). This represents a group of patients in whom mortality at D+100 has been estimated to be >80%.
Comparisons: The primary parameter is Complete Response at 100 days following stem cell transplant, utilizing historical controls as a comparator. The historical control database will be generated through a retrospective medical chart review performed at participating centers; the survival outcome of patients who would otherwise have met eligiblity criteria for this trial will be compared to the survival observed in patients prospectively treated with defibrotide. Secondary parameters include survival rate at 100 days and 6 months post SCT, and special studies of endothelial and serum markers for VOD. This study will assess safety of the dose and schedule in this setting.