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

Hepatic Veno-Occlusive Disease Clinical Trial

— VOD-DF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00272948
• Other study ID #: EudraCT Number:2004-000592-33
• Secondary ID: EBMT-PD-200601
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 4, 2006
• Last updated: June 8, 2011
• Start date: December 2005
• Est. completion date: July 2009

Study information

• Verified date: June 2011
• Source: European Group for Blood and Marrow Transplantation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and WomenFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesIreland: Irish Medicines BoardItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthIsrael: Israeli Health Ministry Pharmaceutical Administrationthe Netherlands: Central Committee on Research Involving Human SubjectsSweden: Medical Products AgencySwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: July 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Budd-Chiari Syndrome
• Hepatic Veno-Occlusive Disease

Intervention

Drug:
• Defibrotide
Defibrotide 25 mg/kg/d
• 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.
• Defibrotide
Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria

Locations

Country	Name	City	State
Austria	University Hospital	Graz
Austria	St Anna Kinderspital	Wien
France	Inst. Gustave Roussy	Villejuif
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
Ireland	Our Lady's Hospital for Sick Children	Dublin
Israel	Schneider Children's MC	Petach-Tikva
Italy	Institute G. Gaslini	Genova
Italy	Ospedale S. Gerardo	Monza
Italy	Clinica di Oncoematologia Pediatrica	Padova
Netherlands	University Hospital	Utrecht
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	University Hospital	Huddinge
Sweden	University Hospital	Lund
Sweden	University Hospital	Uppsala
Switzerland	University Children Hospital	Basel
Switzerland	Inselspital	Bern
Switzerland	Hopital Cantonal Universitaire	Geneva
Switzerland	University Hospital	Zürich
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Children's Hospital	Manchester

Sponsors (3)

Lead Sponsor	Collaborator
European Group for Blood and Marrow Transplantation	Deutsche Krebshilfe e.V., Bonn (Germany), Jazz Pharmaceuticals

Countries where clinical trial is conducted

Austria,  France,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD		Day + 30 post HSCT	No
Secondary	Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)		day +100 post HSCT	Yes

External Links

•   sponsor's Web site