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

Hepatic Veno-Occlusive Disease Clinical Trial

— Treatment IND  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00628498
• Other study ID #: P2006-05
• Status: Completed
• Phase: Phase 3
• First received: February 25, 2008
• Last updated: November 2, 2017
• Start date: December 2007
• Est. completion date: September 2016

Study information

• Verified date: November 2017
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1206
• Est. completion date: September 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Veno-Occlusive Disease

Intervention

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.
• Defibrotide

Locations

Country	Name	City	State
United States	Children's Hospital Medical	Akron	Ohio
United States	Presbyterian Hospital	Albuquerque	New Mexico
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Childrens Healthcare of Atlanta	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland - Greenebaum Cancer Center	Baltimore	Maryland
United States	National Institutes of Health	Bethesda	Maryland
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Children's Hospital DFCI/CHB-Pediatrics	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Northwest Memorial Hospital	Chicago	Illinois
United States	Pediatric Hematology/Oncology MC4060 - University of Chicago	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Jewish Hospital	Cincinnati	Ohio
United States	Case Western Reserve University (Cwru) - University Hospitals of Cleveland (Uhc)	Cleveland	Ohio
United States	Robert J Tomsich Pathology & Laboratory Medicine Institute	Cleveland	Ohio
United States	Nationwide Children's Hospital - Ohio State University College of Medicine (OSUCOM)	Columbus	Ohio
United States	The Ohio State University, James Cancer Hospital	Columbus	Ohio
United States	Children's Medical Center of Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	US Oncology - Denver	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Children's Hospital of Michigan	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	Cook Children's Health Care Hospital	Fort Worth	Texas
United States	UF Health Shands Hospital	Gainesville	Florida
United States	Helen DeVos Children's Hospital - Spectrum Health	Grand Rapids	Michigan
United States	Greenville Health System Cancer Institute	Greenville	South Carolina
United States	Hackensack University Medical Center - Joseph M. Sanzari Childrens Hospital	Hackensack	New Jersey
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kapi'olani Medical Center for Women and Children	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana Blood and Marrow Transplantation Clinical Lab LLC/St. Francis Hospital	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital and Clinics - Infectious Diseases	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	The University of California, San Diego	La Jolla	California
United States	University of Arkansas for Medical Services	Little Rock	Arkansas
United States	Loma Linda University	Loma Linda	California
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Pediatric Blood and Cancer Disorders Clinic	Louisville	Kentucky
United States	University of Louisville Research Foundation	Louisville	Kentucky
United States	University of Wisconsin, American Family Children's Hospital, Medical School	Madison	Wisconsin
United States	Cardinal Bernardin Cancer-Loyola University Medical Center	Maywood	Illinois
United States	Methodist University Hospital	Memphis	Tennessee
United States	St. Jude Children's Research Hospital - Department of Bone Marrow Transplantation and Cellular Therapy	Memphis	Tennessee
United States	Jackson Memorial- University of Miami Health System- Pediatrics	Miami	Florida
United States	Nicklaus Children's Hospital (Miami Children's Hospital)	Miami	Florida
United States	Medical College of Wisconsin/ Children's Hospitalof Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota and Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Mary Babb Randolph Cancer Center - West Virginia University Hospital	Morgantown	West Virginia
United States	The Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale - New Haven Hospital	New Haven	Connecticut
United States	Steven and Alexandra Cohen Children's Medical Center	New Hyde Park	New York
United States	Children's Hospital	New Orleans	Louisiana
United States	Tulane University Hospital & Clinic (Tuhc) - Tulane Cancer Center Comprehensive Clinic (Tcccc)	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Morgan Stanley Children's Hospital - Columbia University Medical Center	New York	New York
United States	Mount Sinai Hospital - BMT Program	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York University School of Medicine	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Children's Hospital of the King's Daughter	Norfolk	Virginia
United States	Children's Hospital & Research Center Oakland	Oakland	California
United States	The University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County (CHOC)	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	West Penn Allegheny Health System	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital - Oregon Health and Science University	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center, Strong Memorial Hospital	Rochester	New York
United States	Sutter Institute for Medical Research	Sacramento	California
United States	University of California Davis Health System	Sacramento	California
United States	Cardinal Glennon Children's Medical Center/St. Louis University Department of Pediatrics	Saint Louis	Missouri
United States	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri
United States	All Children's Hospital Specialty Physicians	Saint Petersburg	Florida
United States	University of Utah	Salt Lake City	Utah
United States	Methodist Healthcare System of San Antonio	San Antonio	Texas
United States	Rady's Children's Hospital - San Diego	San Diego	California
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Arizona Oncology	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center/Seattle Children Hospital	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Stanford University Medical Center	Stanford	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Montefiore Medical Center	The Bronx	New York
United States	University Medical Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Nemours-Al duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival by Day+100 Post Stem Cell Transplant or Chemotherapy		Day +100 from HSCT or 100 days from start of chemotherapy