Clinical trial NCT00272948: Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hepatic Veno-Occlusive Disease
Keywords: Venoocclusive disease
Pediatric
myeloablative conditioning
stem cell transplant
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Jazz Pharmaceuticals
name: Deutsche Krebshilfe e.V., Bonn (Germany)
First posted: 2006-01-09
Enrollment: 360
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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 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

Primary outcomes:
measure: The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
timeFrame: Day + 30 post HSCT
Secondary outcomes:
measure: Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)
timeFrame: day +100 post HSCT
Other outcomes:
Locations:
city: Graz
country: Austria
facility: University Hospital
city: Wien
country: Austria
facility: St Anna Kinderspital
city: Villejuif
country: France
facility: Inst. Gustave Roussy
city: Dresden
country: Germany
facility: University Hospital
city: Düsseldorf
country: Germany
facility: Klinik Kinder-Onkologie
city: Frankfurt
country: Germany
facility: Johann-Wolfgang Goethe Universität
city: Hamburg
country: Germany
facility: Universitätsspital Eppendorf
city: Hannover
country: Germany
facility: Medical School
city: Heidelberg
country: Germany
facility: University Hospital
city: Jena
country: Germany
facility: Kinderklinik
city: Kiel
country: Germany
facility: Christian-Albrecht -University
city: München
country: Germany
facility: Kinderpoliklinik Uni
city: Münster
country: Germany
facility: Poliklinik Kinderheilkunde
city: Tübingen
country: Germany
facility: Universitätsspital
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children
city: Petach-Tikva
country: Israel
facility: Schneider Children's MC
city: Genova
country: Italy
facility: Institute G. Gaslini
city: Monza
country: Italy
facility: Ospedale S. Gerardo
city: Padova
country: Italy
facility: Clinica di Oncoematologia Pediatrica
city: Utrecht
country: Netherlands
facility: University Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Huddinge
country: Sweden
facility: University Hospital
city: Lund
country: Sweden
facility: University Hospital
city: Uppsala
country: Sweden
facility: University Hospital
city: Basel
country: Switzerland
facility: University Children Hospital
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire
city: Zürich
country: Switzerland
facility: University Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Children's Hospital
Study officials:
affiliation: University of Ulm, Germany
name: Selim Corbacioglu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, Boelens JJ, Hewitt A, Schrum J, Schulz AS, Muller I, Stein J, Wynn R, Greil J, Sykora KW, Matthes-Martin S, Fuhrer M, O'Meara A, Toporski J, Sedlacek P, Schlegel PG, Ehlert K, Fasth A, Winiarski J, Arvidson J, Mauz-Korholz 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.