Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients
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 VOD through the analysis of blood samples.
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.
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Severe Hepatic Veno Occlusive Disease
Intervention
Defibrotide
Location
Duarte
California
United States
Status
Completed
Source
Gentium SpA
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00358501
- Information obtained from ClinicalTrials.gov on July 18, 2011
Medical and Biotech [MESH] Definitions
Hepatic Veno-occlusive Disease
Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.
Pulmonary Veno-occlusive Disease
Pathological process resulting in the fibrous obstruction of the small- and medium-sized PULMONARY VEINS and PULMONARY HYPERTENSION. Veno-occlusion can arise from fibrous proliferation of the VASCULAR INTIMA and VASCULAR MEDIA; THROMBOSIS; or a combination of both.
Hepatic Insufficiency
Conditions in which the LIVER functions fall below the normal ranges. Severe hepatic insufficiency may cause LIVER FAILURE or DEATH. Treatment may include LIVER TRANSPLANTATION.
Glycogen Storage Disease Type Vi
A hepatic GLYCOGEN STORAGE DISEASE in which there is an apparent deficiency of hepatic phosphorylase (GLYCOGEN PHOSPHORYLASE, LIVER FORM) activity.
Liver Failure, Acute
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Clinical Trials
The aim of this trial is to evaluate whether the prophylactic use of Defibrotide (DF) in pediatric patients (age less than 18 years) undergoing stem cell transplantation and who are at hig...
Compassionate Use of Defibrotide for Patients With Veno-occlusive Disease of the Liver
Veno-occlusive disease (VOD) of the liver is a significant complication for some patients undergoing hematopoietic stem cell transplantation. This disease is thought to be a toxicity secon...
Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation
RATIONALE: Giving defibrotide may be an effective treatment for liver damage that may result following peripheral stem cell transplantation. PURPOSE: This randomized phase II trial is stu...
Safety and Tolerability of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease
The primary objective is to evaluate safety and tolerability of single and repeated administrations of escalating doses of NV1FGF administered intramuscularly in patients with severe Perip...
Efficacy and Safety Study of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease.
Peripheral Arterial Occlusive Disease (PAOD) is a condition caused by ischemia in the legs due to atherosclerotic disease affecting the larger arteries of the legs. Chronic PAOD can be reg...
PubMed Articles
Prophylactic use of defibrotide (DF) to prevent veno-occlusive disease (VOD), a relatively common and high-risk complication of hematopoietic stem cell transplantation (HSCT), may be an encouraging mo...
Pulmonary veno-occlusive disease (PVOD) is a rare and usually survival poor disorder. We report a patient with a long history of progressive dyspnea of over 8 years, who with a diagnosis of chronic co...
Aim: We conducted this study to evaluate the role of multidetector computed tomography (MDCT) in diagnosing and differential diagnosis hepatic veno-occlusive disease (HVOD), and as well as assessin...
Hepatic veno-occlusive disease (HVOD) is a life-threatening complication of bone marrow stem cell transplantation. The understanding of this clinical condition is hampered by the lack of suitable anim...
