This trial is active, not recruiting.

Condition veno-occlusive disease
Treatment defibrotide
Phase phase 2
Sponsor Dana-Farber Cancer Institute
Collaborator National Cancer Institute (NCI)
Start date March 1999
Trial size 140 participants
Trial identifier NCT00003966, CDR0000067166, CHNMC-02118, DFCI-1999-P-010076/14, DFCI-99118, DUMC-00176-00-2, FHCRC-1375.00, JHMI-00-06-02-02, MSKCC-03-058, NCI-G99-1548


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Primary purpose supportive care

Primary Outcomes

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)
time frame:

Secondary Outcomes

Survival at 100 days following stem cell transplantation
time frame:
Toxicity by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion
time frame:
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
time frame:
Occurrence of other adverse events by NCI Common Toxicity Criteria version 2.0 during study and 30 days after study completion
time frame:
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
time frame:
Feasibility of pharmacokinetics (PK) across dose arms and the PK of defibrotide by PK analysis
time frame:

Eligibility Criteria

Male or female participants of any age.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2009.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).