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

• Sponsor: European Society for Blood and Marrow Transplantation (Other)
• Overall Status: Completed
• CT.gov ID: NCT00272948
• Collaborator: Jazz Pharmaceuticals (Industry), Deutsche Krebshilfe e.V., Bonn (Germany) (Other)
• Enrollment: 360
• Locations: 30
• Arms: 2
• Duration (Months): 43
• Patients Per Site: 12
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Veno-Occlusive Disease	Drug: Defibrotide; Drug: Defibrotide; Drug: Defibrotide	Phase 2/Phase 3

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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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 Start Date: Dec 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prophylaxis Arm	Drug: Defibrotide; Defibrotide 25 mg/kg/d; Drug: Defibrotide; 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.
Active Comparator: Control Arm	Drug: Defibrotide; Defibrotide 25 mg/kg/d; Drug: Defibrotide; Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria

Outcome Measures

Primary Outcome Measures

1. The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD [Day + 30 post HSCT]

Secondary Outcome Measures

1. Occurrence of Multi-System Organ Failure and Survival (all causes of mortality) [day +100 post HSCT]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital	Graz		Austria
2	St Anna Kinderspital	Wien		Austria
3	Inst. Gustave Roussy	Villejuif		France
4	University Hospital	Dresden		Germany
5	Klinik Kinder-Onkologie	Düsseldorf		Germany
6	Johann-Wolfgang Goethe Universität	Frankfurt		Germany
7	Universitätsspital Eppendorf	Hamburg		Germany
8	Medical School	Hannover		Germany
9	University Hospital	Heidelberg		Germany
10	Kinderklinik	Jena		Germany
11	Christian-Albrecht -University	Kiel		Germany
12	Kinderpoliklinik Uni	München		Germany
13	Poliklinik Kinderheilkunde	Münster		Germany
14	Universitätsspital	Tübingen		Germany
15	Our Lady's Hospital for Sick Children	Dublin		Ireland
16	Schneider Children's MC	Petach-Tikva		Israel
17	Institute G. Gaslini	Genova		Italy
18	Ospedale S. Gerardo	Monza		Italy
19	Clinica di Oncoematologia Pediatrica	Padova		Italy
20	University Hospital	Utrecht		Netherlands
21	Sahlgrenska University Hospital	Göteborg		Sweden
22	University Hospital	Huddinge		Sweden
23	University Hospital	Lund		Sweden
24	University Hospital	Uppsala		Sweden
25	University Children Hospital	Basel		Switzerland
26	Inselspital	Bern		Switzerland
27	Hopital Cantonal Universitaire	Geneva		Switzerland
28	University Hospital	Zürich		Switzerland
29	Great Ormond Street Hospital	London		United Kingdom
30	Children's Hospital	Manchester		United Kingdom

Sponsors and Collaborators

• European Society for Blood and Marrow Transplantation
• Jazz Pharmaceuticals
• Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

• Principal Investigator: Selim Corbacioglu, MD, University of Ulm, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• sponsor's Web site

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00272948
• Other Study ID Numbers: EudraCT Number:2004-000592-33; EBMT-PD-200601
• First Posted: Jan 9, 2006
• Last Update Posted: Jun 9, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: Venoocclusive disease; Pediatric; myeloablative conditioning; stem cell transplant
• Additional relevant MeSH terms: Hepatic Veno-Occlusive Disease; Defibrotide

Study Results

No Results Posted as of Jun 9, 2011