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

This study has been completed.
Sponsor:
Collaborators:
Gentium SpA
Deutsche Krebshilfe e.V., Bonn (Germany)
Information provided by:
European Group for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier:
NCT00272948
First received: January 4, 2006
Last updated: June 8, 2011
Last verified: June 2011

January 4, 2006
June 8, 2011
December 2005
January 2009   (final data collection date for primary outcome measure)
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 ]
  • The primary objective is to evaluate if prophylactic DF has an impact on the:
  • The aim of this trial is to evaluate prophylactic Defibrotide (DF) in a pediatric patient population at high risk for Veno-occlusive Disease (VOD).
  • - incidence of VOD,
  • - the severity of VOD and
  • - the mortality due to VOD
Complete list of historical versions of study NCT00272948 on ClinicalTrials.gov Archive Site
Occurrence of Multi-System Organ Failure and Survival (all causes of mortality) [ Time Frame: day +100 post HSCT ] [ Designated as safety issue: Yes ]
  • The secondary objectives are to:
  • - evaluate if prophylactic DF compared to the therapeutic use of DF alone is associated with a better long-term survival
  • - evaluate if prophylactic DF has an impact on the incidence of graft-versus-host disease (GvHD
  • - collect data on eventual side effects of DF in the pediatric transplant population
  • - collect data on the potential benefit of DF on the incidence and severity of TTP
Not Provided
Not Provided
 
Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide
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.

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
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Hepatic Veno-Occlusive Disease
  • 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.
  • Drug: Defibrotide
    Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria
  • Experimental: Prophylaxis Arm
    Interventions:
    • Drug: Defibrotide
    • Drug: Defibrotide
  • Active Comparator: Control Arm
    Interventions:
    • Drug: Defibrotide
    • Drug: Defibrotide
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
360
July 2009
January 2009   (final data collection date for primary outcome measure)

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
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Austria,   France,   Germany,   Ireland,   Israel,   Italy,   Netherlands,   Sweden,   Switzerland,   United Kingdom
 
NCT00272948
EudraCT Number:2004-000592-33, EBMT-PD-200601
Yes
Liz Clark, European Group for Blood and Marrow Transplantation
European Group for Blood and Marrow Transplantation
  • Gentium SpA
  • Deutsche Krebshilfe e.V., Bonn (Germany)
Principal Investigator: Selim Corbacioglu, MD University of Ulm, Germany
European Group for Blood and Marrow Transplantation
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP