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

Sponsors and Collaborators:	Gentium SpA FDA Office of Orphan Products Development
Information provided by:	Gentium SpA
ClinicalTrials.gov Identifier:	NCT00358501

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 III

Drug Information available for: Defibrotide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
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

Further study details as provided by Gentium SpA:

Primary Outcome Measures:

Complete Response at D+100 post stem cell transplant

Secondary Outcome Measures:

Survival at D+100 following stem cell transplant
Long-term (6 month) survival rate
Safety of the selected dose and schedule

Estimated Enrollment:	80
Study Start Date:	July 2006

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

FDA Office of Orphan Products Development

More Information

Click here for more information about Defibrotide. This link exits the ClinicalTrials.gov site

Publications:

Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, Avigan D, Bearman SI, Martin PL, Kurtzberg J, Vredenburgh J, Chen AR, Arai S, Vogelsang G, McDonald GB, Guinan EC. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002 Dec 15;100(13):4337-43. Epub 2002 Aug 1.

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).

Study ID Numbers:	2005-01
Study First Received:	July 28, 2006
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00358501
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

Study placed in the following topic categories:

Hepatic venoocclusive disease
Liver Diseases
Digestive System Diseases
Multiple Organ Failure

Vascular Diseases
Defibrotide
Hepatic Veno-Occlusive Disease

Additional relevant MeSH terms:

Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Hematologic Agents
Platelet Aggregation Inhibitors

Fibrinolytic Agents
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009