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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Hepatic Veno-Occlusive Disease

Intervention / Treatment
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* Drug: Defibrotide
* Drug: Defibrotide
* Drug: Defibrotide


Participation Criteria
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Eligibility Criteria
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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: Pre-existing liver disease Second myeloablative HSCT History of treatment with gemtuzumab ozogamicin (MYLOTARGÒ, GO, CMA-676, Wyeth) Allogeneic HSCT for leukemia beyond the second relapse Osteopetrosis (OP) Conditioning with busulfan and melphalan Macrophage activating syndromes (MAS, like hemophagocytic lymphohistiocytosis, Griscelli, Chediak-Higashi Adrenoleukodystrophy (ALD) Exclusion Criteria: Pregnant patients Patients who are transplanted but do not fulfill any of the above mentioned criteria

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylaxis Arm<br> | Drug: Defibrotide<br>* Defibrotide 25 mg/kg/d<br>Drug: Defibrotide<br>* 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.<br>|
| Active Comparator: Control Arm<br> | Drug: Defibrotide<br>* Defibrotide 25 mg/kg/d<br>Drug: Defibrotide<br>* Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venoocclusive disease, Pediatric, myeloablative conditioning, stem cell transplant