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

Conditions

Hepatic Veno-Occlusive Disease

Keywords

Venoocclusive disease, Pediatric, myeloablative conditioning, stem cell transplant

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

Corbacioglu S, Bajwa R, Antmen AB, Balduzzi A, Boelens JJ, Bonifazi F, Cesaro S, Ciceri F, Colecchia A, Dignan F, Kleinschmidt K, Mahadeo KM, Pagliuca A, Sedlacek P, Shaw PJ, Stein J, Szmit Z, Tambaro F, Ince E, Verna M, Yesilipek A, Zecca M, Richardson PG, Mohty M, Kalwak K, EBMT Paediatric Diseases Working Party.

2026-01-13

10.1038/s41409-025-02793-x

Defibrotide for prophylaxis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in pediatric high-risk patients: consensus guidelines from the European Society for Blood and Marrow Transplantation (EBMT)

Selim Corbacioglu, Rajinder Bajwa, Bülent Antmen, Adriana Balduzzi, Rajni Agarwal et al. (25 authors)

University of Regensburg Publication Server (University of Regensburg)2026-01-01

10.5283/epub.78428

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

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.

2012-02-23255 citations

10.1016/s0140-6736(11)61938-7

Interventions

DRUGDefibrotide

Defibrotide 25 mg/kg/d

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 18 Years

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: 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

Design outcomes

Primary

Measure	Time frame
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD	Day + 30 post HSCT

Secondary

Measure	Time frame
Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)	day +100 post HSCT

Countries

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

Outcome results

None listed