Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide (VOD-DF)
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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 |
- 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 ]
- 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 |
| Genders Eligible for Study: | Both |
| 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:
- 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
Contacts and 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 | |
| Principal Investigator: | Selim Corbacioglu, MD | University of Ulm, Germany |
More Information
No publications provided by European Group for Blood and Marrow Transplantation
Additional 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, 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 Budd-Chiari Syndrome Liver Diseases Digestive System Diseases Vascular Diseases Cardiovascular Diseases Venous Thrombosis Thrombosis Embolism and Thrombosis |
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