Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2006 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003966
First received: November 1, 1999
Last updated: May 9, 2009
Last verified: May 2006
  Purpose

RATIONALE: Giving defibrotide may be an effective treatment for liver damage that may result following peripheral stem cell transplantation.

PURPOSE: This randomized phase II trial is studying defibrotide to see how well it works in treating patients with severe liver disease after undergoing peripheral stem cell transplantation.


Condition Intervention Phase
Veno-Occlusive Disease
Drug: defibrotide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Supportive Care
Official Title: Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete Response Rate as measured by a total bilirubin of < 2 mg/dL and resolution of multi-organ failure attributable to veno-occlusive disease (VOD)

Secondary Outcome Measures:
  • Survival at 100 days following stem cell transplantation
  • Toxicity by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion
  • Grade 3-4 end organ dysfunction attributable to defibrotide as determined by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion
  • Occurrence of other adverse events by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion
  • Effect of drug on plasminogen activator inhibitor-1 (PAI-1) determination of dose-relationship between drug and/or VOD response as measured by survival, PAI-1 levels, and research assays at day 100
  • Feasibility of pharmacokinetics (PK) across dose arms and the PK of defibrotide by PK analysis

Estimated Enrollment: 140
Study Start Date: March 1999
Detailed Description:

OBJECTIVES:

  • Determine complete response rate in post-hematopoietic stem cell transplant patients with severe veno-occlusive disease of the liver treated with defibrotide.
  • Determine the minimal effective dose of this drug in these patients.
  • Assess toxicity and adverse side effects of this drug in these patients.

OUTLINE: This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide.

  • Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours.
  • Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours.

In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 140 patients (70 per treatment arm) will be accrued for this study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of veno-occlusive disease (VOD) of the liver after hematopoietic stem cell transplant as evidenced by 1 of the following:

    • Jaundice (bilirubin at least 2 mg/dL) and at least 2 of the following: ascites, weight gain over 5%, hepatomegaly, or right upper quadrant pain
    • Jaundice and reversal of flow on doppler examination of portal vein with at least 1 of the above mentioned criteria
  • Diagnosed no more than 35 days prior to study entry
  • Severity of VOD defined by Bearman model of 30% or more risk of severe disease and/or evidence of multiorgan failure
  • No concurrent grade B-D graft-versus-host disease (based on the International Bone Marrow Transplant Registry Severity Index)

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • See Disease Characteristics

Renal:

  • Not specified

Cardiovascular:

  • Must be hemodynamically stable

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No prior tissue plasminogen activator treatment
  • No other concurrent experimental agent
  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: NCT00003966

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Study Chair: Paul G.G. Richardson, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Richardson PG, Soiffer RJ, Antin JH, et al.: Defibrotide (DF) for the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post SCT: final results of a phase II, multicenter, randomized study and preliminary analyses of surrogate markers and ultrasound findings. [Abstract] Blood 104 (11): A-350, 2004.
Richardson P, Soiffer RJ, Antin JH, et al.: Defibrotide (DF) is effective in the treatment of severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): results of a phase II, multicenter, randomized study. [Abstract] Blood 102 (11): A-674, 2003.
Richardson PG, Soiffer R, Antin JH, et al.: Defibrotide (DF) appears effective and safe in a phase II, randomized study of patients (pts) with severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT). [Abstract] Blood 100 (9): A-414, 2002.

ClinicalTrials.gov Identifier: NCT00003966     History of Changes
Other Study ID Numbers: CDR0000067166, DFCI-99118, DFCI-1999-P-010076/14, DUMC-00176-00-2, FHCRC-1375.00, NCI-G99-1548, CHNMC-02118, MSKCC-03-058, JHMI-00-06-02-02
Study First Received: November 1, 1999
Last Updated: May 9, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
veno-occlusive disease

Additional relevant MeSH terms:
Defibrotide
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014