Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Treatment IND
1 other identifier
interventional
1,206
1 country
125
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2007
Longer than P75 for phase_3
125 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2007
CompletedFirst Submitted
Initial submission to the registry
February 25, 2008
CompletedFirst Posted
Study publicly available on registry
March 5, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2016
CompletedResults Posted
Study results publicly available
November 30, 2017
CompletedNovember 30, 2017
November 1, 2017
8.6 years
February 25, 2008
November 2, 2017
November 2, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
Day +100 from HSCT or 100 days from start of chemotherapy
Study Arms (1)
Defibrotide
EXPERIMENTALDefibrotide 25 mg/kg day given in 4 divided doses approximately every 6 hours
Interventions
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.
Eligibility Criteria
You may qualify if:
- Entry criteria include the following:
- Clinical diagnosis of VOD, made by Baltimore Criteria, Modified Seattle Criteria, or biopsy proven:
- 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.
- 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
- Patients that do not meet the Baltimore Criteria or Modified Seattle Criteria and have biopsy proven VOD are eligible.
- Patient must also provide written informed consent.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (125)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
Mayo Clinic Cancer Center
Phoenix, Arizona, 85054, United States
Arizona Oncology
Scottsdale, Arizona, 85258, United States
University Medical Center
Tucson, Arizona, 85724, United States
University of Arkansas for Medical Services
Little Rock, Arkansas, 72205, United States
City of Hope Medical Center
Duarte, California, 91010, United States
The University of California, San Diego
La Jolla, California, 92037, United States
Loma Linda University
Loma Linda, California, 92354, United States
Long Beach Memorial Medical Center
Long Beach, California, 90806, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital & Research Center Oakland
Oakland, California, 94609, United States
Children's Hospital of Orange County (CHOC)
Orange, California, 92868, United States
Sutter Institute for Medical Research
Sacramento, California, 95816, United States
University of California Davis Health System
Sacramento, California, 95817, United States
Rady's Children's Hospital - San Diego
San Diego, California, 92123, United States
University of California San Francisco Medical Center
San Francisco, California, 94143, United States
Stanford University Medical Center
Stanford, California, 94305, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
US Oncology - Denver
Denver, Colorado, 80218, United States
Yale - New Haven Hospital
New Haven, Connecticut, 06520, United States
Nemours-Al duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
UF Health Shands Hospital
Gainesville, Florida, 32610, United States
Jackson Memorial- University of Miami Health System- Pediatrics
Miami, Florida, 33136, United States
Nicklaus Children's Hospital (Miami Children's Hospital)
Miami, Florida, 33155, United States
Florida Hospital
Orlando, Florida, 42803, United States
All Children's Hospital Specialty Physicians
St. Petersburg, Florida, 33701, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Childrens Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Kapi'olani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Northwest Memorial Hospital
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Pediatric Hematology/Oncology MC4060 - University of Chicago
Chicago, Illinois, 60637, United States
Cardinal Bernardin Cancer-Loyola University Medical Center
Maywood, Illinois, 60153, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Indiana Blood and Marrow Transplantation Clinical Lab LLC/St. Francis Hospital
Indianapolis, Indiana, 46237, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Pediatric Blood and Cancer Disorders Clinic
Louisville, Kentucky, 40202, United States
University of Louisville Research Foundation
Louisville, Kentucky, 40202, United States
Tulane University Hospital & Clinic (Tuhc) - Tulane Cancer Center Comprehensive Clinic (Tcccc)
New Orleans, Louisiana, 70112, United States
Children's Hospital
New Orleans, Louisiana, 70118, United States
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
National Institutes of Health
Bethesda, Maryland, 20892, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Boston Children's Hospital DFCI/CHB-Pediatrics
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109, United States
Wayne State University/Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Helen DeVos Children's Hospital - Spectrum Health
Grand Rapids, Michigan, 49503, United States
Children's Hospitals and Clinics of Minnesota and Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospital and Clinics - Infectious Diseases
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center/St. Louis University Department of Pediatrics
St Louis, Missouri, 63104, United States
Washington University/St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center - Joseph M. Sanzari Childrens Hospital
Hackensack, New Jersey, 07601, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Presbyterian Hospital
Albuquerque, New Mexico, 87106, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Steven and Alexandra Cohen Children's Medical Center
New Hyde Park, New York, 11040, United States
New York University School of Medicine
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10021, United States
Mount Sinai Hospital - BMT Program
New York, New York, 10029, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Morgan Stanley Children's Hospital - Columbia University Medical Center
New York, New York, 10032, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10065, United States
University of Rochester Medical Center, Strong Memorial Hospital
Rochester, New York, 14642, United States
Stony Brook University Hospital
Stony Brook, New York, 11794, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
New York Medical College
Valhalla, New York, 10595, United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
Children's Hospital Medical
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
The Jewish Hospital
Cincinnati, Ohio, 45236, United States
Case Western Reserve University (Cwru) - University Hospitals of Cleveland (Uhc)
Cleveland, Ohio, 44106, United States
Robert J Tomsich Pathology & Laboratory Medicine Institute
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital - Ohio State University College of Medicine (OSUCOM)
Columbus, Ohio, 43205, United States
The Ohio State University, James Cancer Hospital
Columbus, Ohio, 43210, United States
The University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104, United States
Doernbecher Children's Hospital - Oregon Health and Science University
Portland, Oregon, 97239, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15219, United States
West Penn Allegheny Health System
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Greenville Health System Cancer Institute
Greenville, South Carolina, 29605, United States
Avera Cancer Institute
Sioux Falls, South Dakota, 57105, United States
Methodist University Hospital
Memphis, Tennessee, 38104, United States
St. Jude Children's Research Hospital - Department of Bone Marrow Transplantation and Cellular Therapy
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Children's Medical Center of Dallas
Dallas, Texas, 75235, United States
San Antonio Military Medical Center
Fort Sam Houston, Texas, 78234, United States
Cook Children's Health Care Hospital
Fort Worth, Texas, 76104, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
The University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Methodist Healthcare System of San Antonio
San Antonio, Texas, 78229, United States
University of Utah
Salt Lake City, Utah, 84132, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Children's Hospital of the King's Daughter
Norfolk, Virginia, 23507, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Fred Hutchinson Cancer Research Center/Seattle Children Hospital
Seattle, Washington, 98109, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Babb Randolph Cancer Center - West Virginia University Hospital
Morgantown, West Virginia, 26505, United States
University of Wisconsin, American Family Children's Hospital, Medical School
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin/ Children's Hospitalof Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (3)
Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, Avigan D, Bearman SI, Martin PL, Kurtzberg J, Vredenburgh J, Chen AR, Arai S, Vogelsang G, McDonald GB, Guinan EC. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002 Dec 15;100(13):4337-43. doi: 10.1182/blood-2002-04-1216. Epub 2002 Aug 1.
PMID: 12393437RESULTRichardson PG, Smith AR, Kernan NA, Lehmann L, Ryan RJ, Grupp SA. Analysis of Time to Complete Response after Defibrotide Initiation in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021 Jan;27(1):88.e1-88.e6. doi: 10.1016/j.bbmt.2020.09.008. Epub 2020 Sep 17.
PMID: 32950693DERIVEDKernan NA, Grupp S, Smith AR, Arai S, Triplett B, Antin JH, Lehmann L, Shore T, Ho VT, Bunin N, Iacobelli M, Liang W, Hume R, Tappe W, Soiffer R, Richardson P. Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Br J Haematol. 2018 Jun;181(6):816-827. doi: 10.1111/bjh.15267. Epub 2018 May 16.
PMID: 29767845DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Associate Director, Clinical Trial Disclosure & Transparency
- Organization
- Jazz Pharmaceuticals
Study Officials
- STUDY CHAIR
William Tappe, M.D.
Jazz Pharmaceuticals
- PRINCIPAL INVESTIGATOR
Paul Richardson, M.D.
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 25, 2008
First Posted
March 5, 2008
Study Start
December 1, 2007
Primary Completion
July 1, 2016
Study Completion
September 1, 2016
Last Updated
November 30, 2017
Results First Posted
November 30, 2017
Record last verified: 2017-11