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

  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama Recruiting
Birmingham, Alabama, United States, 35233
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
University Medical Center Recruiting
Tucson, Arizona, United States, 85724
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
The University of California, San Diego Recruiting
La Jolla, California, United States, 92037
Long Beach Memorial Medical Center Recruiting
Long Beach, California, United States, 90806
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Children's Hospital & Research Center Oakland Recruiting
Oakland, California, United States, 94609
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
University of California Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Rady Children's Hospital - San Diego Recruiting
San Diego, California, United States, 92123
University of California San Francisco Children's Hospital Recruiting
San Francisco, California, United States, 94143
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
United States, Colorado
The Children's Hospital Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale - New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06520
United States, Delaware
Nemours-Al duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
University of Florida Shands Cancer Center Recruiting
Gainesville, Florida, United States, 32610
Miami Children's Hospital Recruiting
Miami, Florida, United States, 33155
Jackson Memorial- University of Miami Health System- Pediatrics Recruiting
Miami, Florida, United States, 33136
Florida Hospital Recruiting
Orlando, Florida, United States, 42803
All Children's Hospital Recruiting
St Petersburg, Florida, United States, 33701
Moffitt Cancer Center Terminated
Tampa, Florida, United States, 33612
United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Blood & Marrow Transplant Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Emory University Hospital Terminated
Atlanta, Georgia, United States, 30322
United States, Hawaii
Kapi Olani Medical Center for Women and Children Recruiting
Honolulu, Hawaii, United States, 96826
United States, Illinois
Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Northwest Memorial Hospital Terminated
Chicago, Illinois, United States, 60611
University of Chicago Medicine Center Recruiting
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana Bone Marrow Transplantation Recruiting
Beechgrove, Indiana, United States, 46107
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals & Clinics Recruiting
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Cancer Center Terminated
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Kosair Children Hospital Recruiting
Louisville, Kentucky, United States, 40202
United States, Louisiana
Children's Hospital Recruiting
New Orleans, Louisiana, United States, 70118
Tulane University Hospital and Clinic Terminated
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
University of Maryland - Greenbaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Henry Ford Health System Terminated
Detriot, Michigan, United States, 48202
Wayne State University Not yet recruiting
Detroit, Michigan, United States, 48201
Children's Hospital of Michigan Not yet recruiting
Detroit, Michigan, United States, 48201
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Children's Hospitals and Clinics of Minnesota and Minneapolis Recruiting
Saint Paul, Minnesota, United States, 55404
United States, Mississippi
University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
United States, Missouri
Children's Mercy Hospital and Clinics Recruiting
Kansas City, Missouri, United States, 64108
St Louis University/Cardinal Glennon Children's Medical Center Recruiting
St. Louis, Missouri, United States, 63104
Washington University/St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New Mexico
Presbyterian Hospital Not yet recruiting
Albequerque, New Mexico, United States, 87106
United States, New York
Roswell Park Cancer Institute Terminated
Buffalo, New York, United States, 14263
Cohen Children's Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
New York Presbyterian Hospital- Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Mount Sinai Hospital Terminated
New York, New York, United States, 10029
New York University School of Medicine Recruiting
New York, New York, United States, 10016
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
New York Medical College Recruiting
Valhalla, New York, United States, 10595
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Levine Children Hospital Recruiting
Charlotte, North Carolina, United States, 28203
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Children's Hospital Medical Recruiting
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
The Jewish Hospital Recruiting
Cincinnati, Ohio, United States, 45236
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
University Hospitals of Cleveland Children Hospital Recruiting
Cleveland, Ohio, United States, 44106
Ohio State University Medical Center Terminated
Columbus, Ohio, United States, 43210
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
United States, Oklahoma
The University of Oklahoma Health Science Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State University - Hershey Children's Hospital Recruiting
Hershey, Pennsylvania, United States, 17033
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15219
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15260
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
United States, South Dakota
Avera Cancer Institute Recruiting
Sioux Falls, South Dakota, United States, 57105
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
Children's Medical Center of Dallas Recruiting
Dallas, Texas, United States, 75235
Cook Children's Health Care Hospital Recruiting
Fort Worth, Texas, United States, 76104
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
MD Anderson Cancer Center Terminated
Houston, Texas, United States, 77030
Methodist Healthcare System of San Antonio Recruiting
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Children's Hospital of the King's Daughter Recruiting
Norfolk, Virginia, United States, 23507
United States, Washington
Seattle Children's Hospital/ University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98105
Fred Hutchinson/Seattle Children Hospital Recruiting
Seattle, Washington, United States, 98109
Providence Sacred Heart Children's Hospital Recruiting
Spokane, Washington, United States, 99204
United States, West Virginia
West Virginia University Hospital Recruiting
Morgantown, West Virginia, United States, 26505
United States, Wisconsin
Medical College of Wisconsin/ Children's Hospitalof Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
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 22, 2014