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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Gentium SpA
ClinicalTrials.gov Identifier:
NCT00358501
First received: July 28, 2006
Last updated: June 21, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Severe Hepatic Veno Occlusive Disease
Drug: Defibrotide
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Gentium SpA:

Primary Outcome Measures:
  • Complete Response at D+100 post stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 102
Study Start Date: July 2006
Study Completion Date: November 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Defibrotide
Defibrotide treatment
Drug: Defibrotide
Defibrotide 6.25 mg/kg i.v. administered four times a day via 2 hour continuous infusion. Minimum duration 21 days.

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of VOD, defined by jaundice (bilirubin >/= 2 mg/dL) and at least 2 of the following clinical findings, by Day +21 post stem cell transplant: ascites; weight gain >/= 5% above baseline weight; hepatomegaly.
  • Severe VOD, defined as VOD with multi-organ failure, i.e., presence of one or both of the following, by Day +28 post stem cell transplant: renal or pulmonary dysfunction.
  • Provide voluntary written informed consent.

Exclusion Criteria:

  • Pre-existing (prior to SCT) cirrhosis
  • An alternative diagnosis for weight gain, ascites and jaundice
  • GVHD grade B or higher involving liver or gut or grade C or higher involving skin
  • Prior solid organ transplant
  • Dependent on dialysis prior to and/or at the time of SCT
  • Dependent on oxygen supplementation prior to SCT
  • Significant acute bleeding or hemodynamic instability
  • Requirement for the use of any medications that increase risk of hemorrhage will be excluded from the treatment group
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00358501

  Show 25 Study Locations
Sponsors and Collaborators
Gentium SpA
Investigators
Principal Investigator: Paul Richardson, M.D. Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Massimo Iacobelli, M.D., Gentium S.p.A.
ClinicalTrials.gov Identifier: NCT00358501     History of Changes
Obsolete Identifiers: NCT00410917
Other Study ID Numbers: 2005-01
Study First Received: July 28, 2006
Last Updated: June 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Gentium SpA:
Defibrotide
Severe veno occlusive disease
Multi organ failure
Stem cell transplant
Liver
Regimen related toxicity
Day 100 survival

Additional relevant MeSH terms:
Hepatic Veno-Occlusive Disease
Budd-Chiari Syndrome
Liver Diseases
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases
Venous Thrombosis
Thrombosis
Embolism and Thrombosis
Defibrotide
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014