Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients
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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 |
- Complete Response at D+100 post stem cell transplant [ Time Frame: Day + 100 post stem cell transplant ] [ Designated as safety issue: No ]
- 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 |
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
Show 25 Study Locations| 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 May 19, 2013