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
Recruitment status was Active, not recruiting
Sponsor:
Dana-Farber Cancer Institute
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
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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 |
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
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 Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Cardiovascular Agents Therapeutic Uses Hematologic Agents Platelet Aggregation Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013