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Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide (VOD-DF)

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ClinicalTrials.gov Identifier: NCT00272948
Recruitment Status : Completed
First Posted : January 9, 2006
Last Update Posted : June 9, 2011
Jazz Pharmaceuticals
Deutsche Krebshilfe e.V., Bonn (Germany)
Information provided by:
European Group for Blood and Marrow Transplantation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatic Veno-Occlusive Disease Drug: Defibrotide Phase 2 Phase 3

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  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : December 2005
Primary Completion Date : January 2009
Study Completion Date : July 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Prophylaxis Arm Drug: Defibrotide
Defibrotide 25 mg/kg/d
Drug: Defibrotide
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.
Active Comparator: Control Arm Drug: Defibrotide
Defibrotide 25 mg/kg/d
Drug: Defibrotide
Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria

Primary Outcome Measures :
  1. The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD [ Time Frame: Day + 30 post HSCT ]

Secondary Outcome Measures :
  1. Occurrence of Multi-System Organ Failure and Survival (all causes of mortality) [ Time Frame: day +100 post HSCT ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

    1. Pre-existing liver disease
    2. Second myeloablative HSCT
    3. History of treatment with gemtuzumab ozogamicin (MYLOTARGÒ, GO, CMA-676, Wyeth)
    4. Allogeneic HSCT for leukemia beyond the second relapse
    5. Osteopetrosis (OP)
    6. Conditioning with busulfan and melphalan
    7. Macrophage activating syndromes (MAS, like hemophagocytic lymphohistiocytosis, Griscelli, Chediak-Higashi
    8. Adrenoleukodystrophy (ALD)

Exclusion Criteria:

  • Pregnant patients
  • Patients who are transplanted but do not fulfill any of the above mentioned criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00272948

University Hospital
Graz, Austria
St Anna Kinderspital
Wien, Austria
Inst. Gustave Roussy
Villejuif, France
University Hospital
Dresden, Germany
Klinik Kinder-Onkologie
Düsseldorf, Germany
Johann-Wolfgang Goethe Universität
Frankfurt, Germany
Universitätsspital Eppendorf
Hamburg, Germany
Medical School
Hannover, Germany
University Hospital
Heidelberg, Germany
Jena, Germany
Christian-Albrecht -University
Kiel, Germany
Kinderpoliklinik Uni
München, Germany
Poliklinik Kinderheilkunde
Münster, Germany
Tübingen, Germany
Our Lady's Hospital for Sick Children
Dublin, Ireland
Schneider Children's MC
Petach-Tikva, Israel
Institute G. Gaslini
Genova, Italy
Ospedale S. Gerardo
Monza, Italy
Clinica di Oncoematologia Pediatrica
Padova, Italy
University Hospital
Utrecht, Netherlands
Sahlgrenska University Hospital
Göteborg, Sweden
University Hospital
Huddinge, Sweden
University Hospital
Lund, Sweden
University Hospital
Uppsala, Sweden
University Children Hospital
Basel, Switzerland
Bern, Switzerland
Hopital Cantonal Universitaire
Geneva, Switzerland
University Hospital
Zürich, Switzerland
United Kingdom
Great Ormond Street Hospital
London, United Kingdom
Children's Hospital
Manchester, United Kingdom
Sponsors and Collaborators
European Group for Blood and Marrow Transplantation
Jazz Pharmaceuticals
Deutsche Krebshilfe e.V., Bonn (Germany)
Principal Investigator: Selim Corbacioglu, MD University of Ulm, Germany

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Liz Clark, European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT00272948     History of Changes
Other Study ID Numbers: EudraCT Number:2004-000592-33
First Posted: January 9, 2006    Key Record Dates
Last Update Posted: June 9, 2011
Last Verified: June 2011

Keywords provided by European Group for Blood and Marrow Transplantation:
Venoocclusive disease
myeloablative conditioning
stem cell transplant

Additional relevant MeSH terms:
Hepatic Veno-Occlusive Disease
Liver Diseases
Digestive System Diseases
Vascular Diseases
Cardiovascular Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors