Clinical trial NCT00628498: Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Official title: Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatic Veno-Occlusive Disease
Keywords: VOD
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-03-05
Enrollment: 1206
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Survival by Day+100 Post Stem Cell Transplant or Chemotherapy
timeFrame: Day +100 from HSCT or 100 days from start of chemotherapy
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology
state: Arizona
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Services
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: La Jolla
country: United States
facility: The University of California, San Diego
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County (CHOC)
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Diego
country: United States
facility: Rady's Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: US Oncology - Denver
state: Colorado
city: New Haven
country: United States
facility: Yale - New Haven Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours-Al duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Miami
country: United States
facility: Jackson Memorial- University of Miami Health System- Pediatrics
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital (Miami Children's Hospital)
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital Specialty Physicians
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Childrens Healthcare of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Honolulu
country: United States
facility: Kapi'olani Medical Center for Women and Children
state: Hawaii
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwest Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Pediatric Hematology/Oncology MC4060 - University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer-Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation Clinical Lab LLC/St. Francis Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Pediatric Blood and Cancer Disorders Clinic
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Research Foundation
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Hospital & Clinic (Tuhc) - Tulane Cancer Center Comprehensive Clinic (Tcccc)
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland - Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital DFCI/CHB-Pediatrics
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Children's Hospital of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital - Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota and Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics - Infectious Diseases
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center/St. Louis University Department of Pediatrics
state: Missouri
city: Saint Louis
country: United States
facility: Washington University/St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center - Joseph M. Sanzari Childrens Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: Presbyterian Hospital
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: Steven and Alexandra Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital - BMT Program
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital - Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center, Strong Memorial Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: The Jewish Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University (Cwru) - University Hospitals of Cleveland (Uhc)
state: Ohio
city: Cleveland
country: United States
facility: Robert J Tomsich Pathology & Laboratory Medicine Institute
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital - Ohio State University College of Medicine (OSUCOM)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University, James Cancer Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Science Center
state: Oklahoma
city: Portland
country: United States
facility: Doernbecher Children's Hospital - Oregon Health and Science University
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Allegheny Health System
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital - Department of Bone Marrow Transplantation and Cellular Therapy
state: Tennessee
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Health Care Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughter
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/Seattle Children Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center - West Virginia University Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin, American Family Children's Hospital, Medical School
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/ Children's Hospitalof Wisconsin
state: Wisconsin
Study officials:
affiliation: Jazz Pharmaceuticals
name: William Tappe, M.D.
role: STUDY_CHAIR
affiliation: Dana-Farber Cancer Institute
name: Paul Richardson, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Richardson 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.
citation: Kernan 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.