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

This study has been completed.
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Jazz Pharmaceuticals Identifier:
First received: July 28, 2006
Last updated: February 2, 2016
Last verified: June 2011
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
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 Jazz Pharmaceuticals:

Primary Outcome Measures:
  • Complete Response at D+100 post stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ]

Secondary Outcome Measures:
  • Survival at D+100 following stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ]
  • Long-term (6 month) survival rate [ Time Frame: 180 days post stem cell transplant ]
  • Safety of the selected dose and schedule [ Time Frame: through 30 days from the last dose of Defibrotide ]

Enrollment: 102
Study Start Date: July 2006
Study Completion Date: March 2015
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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00358501

  Show 29 Study Locations
Sponsors and Collaborators
Jazz Pharmaceuticals
FDA Office of Orphan Products Development
Principal Investigator: Paul Richardson, M.D. Dana-Farber Cancer Institute
  More Information

Richardson, Soiffer, Antin, Voss, Jin, Kurtzberget al. Defibrotide (DF) for the Treatment of Severe Veno-Occlusive Disease (VOD) and Multi-System Organ Failure (MOF) Post SCT: Final Results of a Phase II, Multicenter, Randomized Study and Preliminary Analyses of Surrogate Markers and Ultrasound Findings. [abstract]. Blood. 2004;104 (11).

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Jazz Pharmaceuticals Identifier: NCT00358501     History of Changes
Obsolete Identifiers: NCT00410917
Other Study ID Numbers: 2005-01 
Study First Received: July 28, 2006
Last Updated: February 2, 2016

Keywords provided by Jazz Pharmaceuticals:
Severe veno occlusive disease
Multi organ failure
Stem cell transplant
Regimen related toxicity
Day 100 survival

Additional relevant MeSH terms:
Hepatic Veno-Occlusive Disease
Liver Diseases
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors processed this record on January 23, 2017