Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide (VOD-DF)
June 8, 2011 updated by: European Society for Blood and Marrow Transplantation
Prospective Randomized Study of the Incidence and Outcome of Veno-Occlusive Disease (VOD) With the Prophylactic Use of Defibrotide (DF) in Pediatric Stem Cell Transplantation
The aim of this trial is to evaluate whether the prophylactic use of Defibrotide (DF) in pediatric patients (age less than 18 years) undergoing stem cell transplantation and who are at high risk of developing hepatic Veno-occlusive Disease (VOD) will have an impact on the incidence and severity of the disease.
Patients will be randomly assigned to one of two treatment arms: Those allocated to the Prophylactic Arm will receive the study drug (Defibrotide) from the day of conditioning onwards.
Patients allocated to the Control Arm will receive the study drug (Defibrotide) from the day that VOD is diagnosed.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Comparison/control intervention and duration of the intervention:
Patients will be assigned randomly to either the Defibrotide (DF) prophylaxis arm or the control arm. Those allocated to the DF prophylaxis arm (DF 25 mg/kg/d iv in 4 doses) will begin treatment at day of conditioning and stop at day +30 after Stem Cell Transplantation (SCT) or upon discharge from inpatient care. There is no dose adjustment for a patient of the study arm who developed VOD, they continue with the 25mg/kg/d iv.
Patients allocated to the control arm receive no prophylactic measures and will start DF (25 mg/kg/d iv in 4 doses) beginning at day of diagnosis of Veno-occlusive Disease (VOD) according to modified Seattle criteria. Treatment will be stopped at complete resolution of symptoms. In both arms patients who developed VOD will continue DF until:
- complete resolution of the ascites and
- reversion of the hepatopedal flow (if present) and
- normalization of the total and direct bilirubin
Study Type
Interventional
Enrollment (Anticipated)
360
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Graz, Austria
- University Hospital
-
Wien, Austria
- St Anna Kinderspital
-
-
-
-
-
Villejuif, France
- Inst. Gustave Roussy
-
-
-
-
-
Dresden, Germany
- University Hospital
-
Düsseldorf, Germany
- Klinik Kinder-Onkologie
-
Frankfurt, Germany
- Johann-Wolfgang Goethe Universität
-
Hamburg, Germany
- Universitätsspital Eppendorf
-
Hannover, Germany
- medical school
-
Heidelberg, Germany
- University Hospital
-
Jena, Germany
- Kinderklinik
-
Kiel, Germany
- Christian-Albrecht -University
-
München, Germany
- Kinderpoliklinik Uni
-
Münster, Germany
- Poliklinik Kinderheilkunde
-
Tübingen, Germany
- Universitätsspital
-
-
-
-
-
Dublin, Ireland
- Our Lady's Hospital for Sick Children
-
-
-
-
-
Petach-Tikva, Israel
- Schneider Children's MC
-
-
-
-
-
Genova, Italy
- Institute G. Gaslini
-
Monza, Italy
- Ospedale S. Gerardo
-
Padova, Italy
- Clinica di Oncoematologia Pediatrica
-
-
-
-
-
Utrecht, Netherlands
- University Hospital
-
-
-
-
-
Göteborg, Sweden
- Sahlgrenska University Hospital
-
Huddinge, Sweden
- University Hospital
-
Lund, Sweden
- University Hospital
-
Uppsala, Sweden
- University Hospital
-
-
-
-
-
Basel, Switzerland
- University Children Hospital
-
Bern, Switzerland
- Inselspital
-
Geneva, Switzerland
- Hôpital Cantonal Universitaire
-
Zürich, Switzerland
- University Hospital
-
-
-
-
-
London, United Kingdom
- Great Ormond Street Hospital
-
Manchester, United Kingdom
- Children's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age <18 years
myeloablative conditioning and autologous or allogeneic stem cell transplantation with at least one of the following risk factors for VOD:
- Pre-existing liver disease
- Second myeloablative HSCT
- History of treatment with gemtuzumab ozogamicin (MYLOTARGÒ, GO, CMA-676, Wyeth)
- Allogeneic HSCT for leukemia beyond the second relapse
- Osteopetrosis (OP)
- Conditioning with busulfan and melphalan
- Macrophage activating syndromes (MAS, like hemophagocytic lymphohistiocytosis, Griscelli, Chediak-Higashi
- Adrenoleukodystrophy (ALD)
Exclusion Criteria:
- Pregnant patients
- Patients who are transplanted but do not fulfill any of the above mentioned criteria
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Control Arm
|
Defibrotide 25 mg/kg/d
Defibrotide 25 mg/kg/d iv in 4 doses beginning at day of conditioning until day +30 or until discharge from inpatient care (with a minimum treatment of 14 days) if VOD does not occur.
Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria
|
|
Experimental: Prophylaxis Arm
|
Defibrotide 25 mg/kg/d
Defibrotide 25 mg/kg/d iv in 4 doses beginning at day of conditioning until day +30 or until discharge from inpatient care (with a minimum treatment of 14 days) if VOD does not occur.
Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
Time Frame: Day + 30 post HSCT
|
Day + 30 post HSCT
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)
Time Frame: day +100 post HSCT
|
day +100 post HSCT
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Selim Corbacioglu, MD, University of Ulm, Germany
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2005
Primary Completion (Actual)
January 1, 2009
Study Completion (Actual)
July 1, 2009
Study Registration Dates
First Submitted
January 4, 2006
First Submitted That Met QC Criteria
January 4, 2006
First Posted (Estimate)
January 9, 2006
Study Record Updates
Last Update Posted (Estimate)
June 9, 2011
Last Update Submitted That Met QC Criteria
June 8, 2011
Last Verified
June 1, 2011
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EudraCT Number:2004-000592-33
- EBMT-PD-200601
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.