Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide - Full Text View

Purpose

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	Intervention	Phase
Hepatic Veno-Occlusive Disease	Drug: Defibrotide	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Hepatic Veno-occlusive Disease

U.S. FDA Resources

Further study details as provided by European Group for Blood and Marrow Transplantation:

Primary Outcome Measures:

The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD [ Time Frame: Day + 30 post HSCT ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence of Multi-System Organ Failure and Survival (all causes of mortality) [ Time Frame: day +100 post HSCT ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	360
Study Start Date:	December 2005
Study Completion Date:	July 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Eligibility


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

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00272948

Locations


Austria
University Hospital
Graz, Austria
St Anna Kinderspital
Wien, Austria
France
Inst. Gustave Roussy
Villejuif, France
Germany
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
Kinderklinik
Jena, Germany
Christian-Albrecht -University
Kiel, Germany
Kinderpoliklinik Uni
München, Germany
Poliklinik Kinderheilkunde
Münster, Germany
Universitätsspital
Tübingen, Germany
Ireland
Our Lady's Hospital for Sick Children
Dublin, Ireland
Israel
Schneider Children's MC
Petach-Tikva, Israel
Italy
Institute G. Gaslini
Genova, Italy
Ospedale S. Gerardo
Monza, Italy
Clinica di Oncoematologia Pediatrica
Padova, Italy
Netherlands
University Hospital
Utrecht, Netherlands
Sweden
Sahlgrenska University Hospital
Göteborg, Sweden
University Hospital
Huddinge, Sweden
University Hospital
Lund, Sweden
University Hospital
Uppsala, Sweden
Switzerland
University Children Hospital
Basel, Switzerland
Inselspital
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)

Investigators


Principal Investigator:	Selim Corbacioglu, MD	University of Ulm, Germany

More Information

Additional Information:

sponsor's Web site This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, Boelens JJ, Hewitt A, Schrum J, Schulz AS, Müller I, Stein J, Wynn R, Greil J, Sykora KW, Matthes-Martin S, Führer M, O'Meara A, Toporski J, Sedlacek P, Schlegel PG, Ehlert K, Fasth A, Winiarski J, Arvidson J, Mauz-Körholz C, Ozsahin H, Schrauder A, Bader P, Massaro J, D'Agostino R, Hoyle M, Iacobelli M, Debatin KM, Peters C, Dini G. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012 Apr 7;379(9823):1301-9. doi: 10.1016/S0140-6736(11)61938-7. Epub 2012 Feb 23.


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 EBMT-PD-200601
Study First Received:	January 4, 2006
Last Updated:	June 8, 2011
Health Authority:	Austria: Federal Ministry for Health and Women France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Ireland: Irish Medicines Board Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Israel: Israeli Health Ministry Pharmaceutical Administration the Netherlands: Central Committee on Research Involving Human Subjects Sweden: Medical Products Agency Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Group for Blood and Marrow Transplantation:


Venoocclusive disease Pediatric myeloablative conditioning stem cell transplant

Additional relevant MeSH terms:


Hepatic Veno-Occlusive Disease Liver Diseases Digestive System Diseases Vascular Diseases Cardiovascular Diseases	Defibrotide Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016

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