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

November 2, 2017 updated by: Jazz Pharmaceuticals
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1206

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Children's Hospital of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Cancer Center
      • Scottsdale, Arizona, United States, 85258
        • Arizona Oncology
      • Tucson, Arizona, United States, 85724
        • University Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas For Medical Services
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
      • La Jolla, California, United States, 92037
        • The University of California, San Diego
      • Loma Linda, California, United States, 92354
        • Loma Linda University
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital of Los Angeles
      • Oakland, California, United States, 94609
        • Children's Hospital & Research Center Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County (CHOC)
      • Sacramento, California, United States, 95816
        • Sutter Institute for Medical Research
      • Sacramento, California, United States, 95817
        • University of California Davis Health System
      • San Diego, California, United States, 92123
        • Rady's Children's Hospital - San Diego
      • San Francisco, California, United States, 94143
        • University of California San Francisco Medical Center
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Denver, Colorado, United States, 80218
        • US Oncology - Denver
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale - New Haven Hospital
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Nemours-Al duPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Hospital
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Health Shands Hospital
      • Miami, Florida, United States, 33136
        • Jackson Memorial- University of Miami Health System- Pediatrics
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital (Miami Children's Hospital)
      • Orlando, Florida, United States, 42803
        • Florida Hospital
      • Saint Petersburg, Florida, United States, 33701
        • All Children's Hospital Specialty Physicians
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Atlanta, Georgia, United States, 30322
        • Childrens Healthcare of Atlanta
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapi'olani Medical Center for Women and Children
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwest Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • Pediatric Hematology/Oncology MC4060 - University of Chicago
      • Maywood, Illinois, United States, 60153
        • Cardinal Bernardin Cancer-Loyola University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46237
        • Indiana Blood and Marrow Transplantation Clinical Lab LLC/St. Francis Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals & Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Pediatric Blood and Cancer Disorders Clinic
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Research Foundation
    • Louisiana
      • New Orleans, Louisiana, United States, 70118
        • Children's Hospital
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Hospital & Clinic (Tuhc) - Tulane Cancer Center Comprehensive Clinic (Tcccc)
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201
        • University of Maryland - Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital DFCI/CHB-Pediatrics
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Children's Hospital of Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital - Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University Of Minnesota Medical Center
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota and Minneapolis
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital and Clinics - Infectious Diseases
      • Saint Louis, Missouri, United States, 63110
        • Washington University/St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Medical Center/St. Louis University Department of Pediatrics
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center - Joseph M. Sanzari Childrens Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Presbyterian Hospital
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, United States, 11040
        • Steven and Alexandra Cohen Children's Medical Center
      • New York, New York, United States, 10016
        • New York University School of Medicine
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical College - New York Presbyterian Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Hospital - BMT Program
      • New York, New York, United States, 10032
        • Morgan Stanley Children's Hospital - Columbia University Medical Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center, Strong Memorial Hospital
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Hospital
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • The University of North Carolina at Chapel Hill
      • Charlotte, North Carolina, United States, 28203
        • Levine Children's Hospital
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Ohio
      • Akron, Ohio, United States, 44308
        • Children's Hospital Medical
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cincinnati, Ohio, United States, 45236
        • The Jewish Hospital
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University (Cwru) - University Hospitals of Cleveland (Uhc)
      • Cleveland, Ohio, United States, 44195
        • Robert J Tomsich Pathology & Laboratory Medicine Institute
      • Columbus, Ohio, United States, 43210
        • The Ohio State University, James Cancer Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital - Ohio State University College of Medicine (OSUCOM)
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • The University of Oklahoma Health Science Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
      • Portland, Oregon, United States, 97239
        • Doernbecher Children's Hospital - Oregon Health and Science University
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033
        • Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15219
        • Children's Hospital of Pittsburgh of UPMC
      • Pittsburgh, Pennsylvania, United States, 15224
        • West Penn Allegheny Health System
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Health System Cancer Institute
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Methodist University Hospital
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital - Department of Bone Marrow Transplantation and Cellular Therapy
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75235
        • Children's Medical Center of Dallas
      • Fort Sam Houston, Texas, United States, 78234
        • San Antonio Military Medical Center
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Health Care Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
      • Houston, Texas, United States, 77030
        • The University of Texas - MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Methodist Healthcare System of San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughter
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/Seattle Children Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center and Children's Hospital
    • West Virginia
      • Morgantown, West Virginia, United States, 26505
        • Mary Babb Randolph Cancer Center - West Virginia University Hospital
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin, American Family Children's Hospital, Medical School
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin/ Children's Hospitalof Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Defibrotide
Defibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Drug: Defibrotide

Defibrotide is a single-stranded polydeoxyribonucleotide derived from porcine intestinal mucosa by controlled depolymerisation. 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
Time Frame: Day +100 from HSCT or 100 days from start of chemotherapy
Day +100 from HSCT or 100 days from start of chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jazz Pharmaceuticals

Investigators

  • Study Chair: William Tappe, M.D., Jazz Pharmaceuticals
  • Principal Investigator: Paul Richardson, M.D., Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

February 25, 2008

First Submitted That Met QC Criteria

March 4, 2008

First Posted (Estimate)

March 5, 2008

Study Record Updates

Last Update Posted (Actual)

November 30, 2017

Last Update Submitted That Met QC Criteria

November 2, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P2006-05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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