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

European Society for Blood and Marrow Transplantation

Status and phase

Completed

Phase 3

Phase 2

Conditions

Hepatic Veno-Occlusive Disease

Treatments

Drug: Defibrotide

Study type

Interventional

Funder types

Other

NETWORK

Industry

Identifiers

NCT00272948

EBMT-PD-200601

EudraCT Number:2004-000592-33

Details and patient eligibility

About

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.

Full 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

Enrollment

360 estimated patients

Sex

All

Ages

Under 18 years old

Volunteers

No Healthy Volunteers

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)