Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Gentium SpA
Sponsor:
Information provided by (Responsible Party):
Gentium SpA
ClinicalTrials.gov Identifier:
NCT00628498
First received: February 25, 2008
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

Single arm, open-label study to provide Defibrotide to patients diagnosed with VOD. Defibrotide is no longer available though the Emergency Use IND mechanism (also known as compassionate use, or single patient named use). This protocol is the only mechanism by which Defibrotide can be made available to patients in the U.S.


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study (Under CFR 312.34)

Resource links provided by NLM:


Further study details as provided by Gentium SpA:

Primary Outcome Measures:
  • Complete response of VOD [ Time Frame: D+100 from SCT or 100 days from start of chemotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Time Frame: D+100 post SCT or 100 days from start of chemotherapy ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: From date study critera were met through 30 days from last Defibrotide dose ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: December 2007
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Defibrotide
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Drug: Defibrotide

Defibrotide is made up of a complex mixture of single stranded oligodeoxyribonucleotides having variable base sequences, chain lengths and molecular weights which form unfolded, folded or combined conformations. Defibrotide has a complex mechanism of action with antithrombotic, anti-ischemic, anti-inflammatory, anti-adhesive and thrombolytic properties but no significant systemic anti-coagulant effects.

Defibrotide is dose intravenously as a 2-hour infusion every 6 hours at a dose of 25 mg/kg/day. Recommended duration of therapy is 21 days.

Drug: Defibrotide

  Eligibility

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

Inclusion Criteria:

Entry criteria include the following:

  1. Clinical diagnosis of VOD, made by Baltimore Criteria, Modified Seattle Criteria, or biopsy proven:

    1.1 Baltimore Criteria- Bilirubin ≥2 mg/dL and at least 2 of the following clinical findings:

    • Ascites (radiographic or physical exam)
    • Weight gain of ≥5% compared to the day of conditioning-- if this value is not available, the weight on the date of admission to the SCT unit may be used)
    • Hepatomegaly; increased over baseline.

    1.2 Modified Seattle Criteria: At least two of the following

    • Bilirubin ≥2 mg/dL
    • Ascites (radiographic or physical exam) and/or weight gain ≥5% above baseline weight (defined as weight on the first day of conditioning- if this value is not available, the weight on the date of admission to the SCT unit may be used)
    • hepatomegaly increased over baseline

    1.3 Patients that do not meet the Baltimore Criteria or Modified Seattle Criteria and have biopsy proven VOD are eligible.

  2. Patient must also provide written informed consent.

Exclusion Criteria:

  • Use of any medication which increases the risk of hemorrhage is disallowed. Use of heparin or other anticoagulants is disallowed within 12 hours unless being used for routine central venous line management, fibrinolytic instillation for central venous line occlusion, intermittent dialysis or ultrafiltration of CVVH.
  • Clinically significant uncontrolled acute bleeding, defined as hemorrhage requiring > 15 cc/kg of packed red blood cells (e.g., a pediatric patient weighing 20 kg and requiring > 300cc of packed red blood cells/24 hours, or an adult patient weighing 70 kg and requiring >3 units of packed red blood cells/24 hours) to replace blood loss, OR bleeding from a site which in the Investigator's opinion constitutes a potential life-threatening source (e.g. pulmonary hemorrhage or CNS bleeding), irrespective of amount of blood loss, at any point from the date of SCT through the date of severe VOD diagnosis.
  • Hemodynamic instability as defined by a requirement for multiple pressors, or inability to maintain mean arterial pressure (for children: to maintain mean arterial pressure within 1 standard deviation of age-adjusted levels) with single pressor support.
  • Woman who are pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628498

Contacts
Contact: Lam Calderon 1.312.706.6240 0265-002Gentium@iconplc.com
Contact: William E Gannon, Jr.,, M.D. 1.202.548.4930 medicalmonitor@gentium.it

  Show 105 Study Locations
Sponsors and Collaborators
Gentium SpA
Investigators
Study Director: Carin Heringa, M.D. Gentium, S.p.A.
Principal Investigator: Paul Richardson, M.D. Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Gentium SpA
ClinicalTrials.gov Identifier: NCT00628498     History of Changes
Other Study ID Numbers: P2006-05
Study First Received: February 25, 2008
Last Updated: January 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gentium SpA:
VOD

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 July 24, 2014