Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose
N/A
N/A
Both
Veno-Occlusive Disease
Trial Information
Defibrotide for Hematopoietic Stem Cell Transplant Patients With Severe Hepatic Venocclusive Disease: A Phase I/II Study to Determine the Minimal Effective Dose
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Supportive Care
Outcome Measure:
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)
Principal Investigator
Paul G.G. Richardson, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000067166
NCT ID:
NCT00003966
Start Date:
March 1999
Completion Date:
Related Keywords:
- Veno-occlusive Disease
- veno-occlusive disease
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
