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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

November 1, 1999
May 9, 2009
March 1999
Not Provided
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)
Not Provided
Complete list of historical versions of study NCT00003966 on ClinicalTrials.gov Archive Site
  • 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
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Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation
Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose

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.

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.

Interventional
Phase 2
Allocation: Randomized
Primary Purpose: Supportive Care
Veno-Occlusive Disease
Drug: defibrotide
Not Provided
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
140
Not Provided
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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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00003966
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
Not Provided
Not Provided
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Study Chair: Paul G.G. Richardson, MD Dana-Farber Cancer Institute
National Cancer Institute (NCI)
May 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP