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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:

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

Sponsor: European Group for Blood and Marrow Transplantation

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

Original Primary Outcome:

  • The aim of this trial is to evaluate prophylactic Defibrotide (DF) in a pediatric patient population at high risk for Veno-occlusive Disease (VOD).
  • The primary objective is to evaluate if prophylactic DF has an impact on the:
  • - incidence of VOD,
  • - the severity of VOD and
  • - the mortality due to VOD


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

Original Secondary Outcome:

  • 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


Information By: European Group for Blood and Marrow Transplantation

Dates:
Date Received: January 4, 2006
Date Started: December 2005
Date Completion:
Last Updated: June 8, 2011
Last Verified: June 2011