Clinical Trial: Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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 veno-occlusive disease (VOD) through the analysis of blood samples.

Detailed Summary:

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 stem cell transplantation (HSCT) 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 multi-organ failure (i.e., pulmonary and/or renal dysfunction). This represents a group of patients in whom mortality at Day+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 eligibility 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 stem cell transplantation (SCT), and special studies of endothelial and serum markers for VOD. This study will assess safety of the dose and schedule in this setting.


Sponsor: Jazz Pharmaceuticals

Current Primary Outcome:

  • Survival at Day+100 Following Hematopoietic Stem Cell Transplant [ Time Frame: Day+100 post hematopoietic stem cell transplant ]
    The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
  • Complete Response by Day+100 Post Hematopoietic Stem Cell Transplant [ Time Frame: Day+100 post hematopoietic stem cell transplant ]
    The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.


Original Primary Outcome: Survival rate at 100 days post stem cell transplant

Current Secondary Outcome:

  • Survival at Day+180 Post Hematopoietic Stem Cell Transplantation [ Time Frame: 180 days post hematopoietic stem cell transplant ]
    The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
  • Percentage of Participants With Treatment-Emergent Adverse Events [ Time Frame: Through 30 days from the last dose of Defibrotide ]


Original Secondary Outcome:

  • Complete response rate (bilirubin less than 2 mg/dL and resolution of MOF)
  • Long-term (6 month) survival rate
  • Safety of the selected dose and schedule


Information By: Jazz Pharmaceuticals

Dates:
Date Received: July 28, 2006
Date Started: July 2006
Date Completion:
Last Updated: December 2, 2016
Last Verified: December 2016