Hepatic Veno-Occlusive DiseasePhase 2/3VOD-DFNCT00272948
Pediatric Trial Investigating the Incidence & Outcome of Veno-Occlusive Disease With the Prophylactic Use of Defibrotide
A Phase 2/3 study testing Defibrotide in people with Hepatic Veno-Occlusive Disease, run by European Society for Blood and Marrow Transplantation at 30 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Hepatic Veno-Occlusive Disease
- What is being tested?
- Defibrotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 30 sitesin 10 countries
- Study dates
- Dec 2005to Jul 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 10Show fewer
- Osteopetrosis (OP)
- Conditioning with busulfan and melphalan
- Macrophage activating syndromes (MAS, like hemophagocytic lymphohistiocytosis, Griscelli, Chediak-Higashi
- Adrenoleukodystrophy (ALD)
Who cannot join
- Pregnant patients
- Patients who are transplanted but do not fulfill any of the above mentioned criteria
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
Germany11 sites
University Hospital
Dresden
Klinik Kinder-Onkologie
Düsseldorf
Johann-Wolfgang Goethe Universität
Frankfurt
Universitätsspital Eppendorf
Hamburg
Medical School
Hanover
University Hospital
Heidelberg
Kinderklinik
Jena
Christian-Albrecht -University
Kiel
Kinderpoliklinik Uni
München
Poliklinik Kinderheilkunde
Münster
Universitätsspital
Tübingen
Sweden4 sites
Sahlgrenska University Hospital
Gothenburg
University Hospital
Huddinge
University Hospital
Lund
University Hospital
Uppsala
Switzerland4 sites
University Children Hospital
Basel
Inselspital
Bern
Hopital Cantonal Universitaire
Geneva
University Hospital
Zurich
Italy3 sites
Institute G. Gaslini
Genova
Ospedale S. Gerardo
Monza
Clinica di Oncoematologia Pediatrica
Padova
United Kingdom2 sites
Great Ormond Street Hospital
London
Children's Hospital
Manchester
About this study
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
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.
Read the 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
- Conditions
- Hepatic Veno-Occlusive Disease
- Being tested
- Defibrotide
- Keywords
- Venoocclusive disease, Pediatric, myeloablative conditioning, stem cell transplant
- Medical subject headings
- Hepatic Veno-Occlusive Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DefibrotideDrug
Defibrotide 25 mg/kg/d
DefibrotideDrug
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.
DefibrotideDrug
Defibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria
| Study group | Role | What they receive |
|---|---|---|
| Prophylaxis Arm | Experimental | Not described Receives: Drug: Defibrotide |
| Control Arm | Active comparator | Not described Receives: Drug: Defibrotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
Measured: Day + 30 post HSCT
Secondary outcomes (1)
Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)
Measured: day +100 post HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startDec 2005
- Primary completionJan 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatic Veno-Occlusive DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 360 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- Jazz Pharmaceuticals, Deutsche Krebshilfe e.V., Bonn (Germany)
- Investigators
- Selim Corbacioglu, MD, Principal investigator, University of Ulm, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272948
- Sponsor's protocol ID
- EudraCT Number:2004-000592-33
- Other IDs
- EBMT-PD-200601
- Acronym
- VOD-DF
- Status last verified
- Jun 2011
- First submitted
- 4 Jan 2006
- Last updated
- 9 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Corbacioglu S, Grupp SA, Richardson PG, Duarte R, Pagliuca A, Ruutu T, Mahadeo K, Carreras E. Prevention of veno-occlusive disease/sinusoidal obstruction syndrome: a never-ending story and no easy answer. Bone Marrow Transplant. 2023 Aug;58(8):839-841. doi: 10.1038/s41409-023-02007-2. Epub 2023 May 25. No abstract available.
PubMed 37231094Corbacioglu 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.
PubMed 22364685
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00272948
- Acronym / sponsor ID
- VOD-DF / EudraCT Number:2004-000592-33
- Conditions
- Hepatic Veno-Occlusive Disease
- Keywords
- Venoocclusive disease, Pediatric, myeloablative conditioning, stem cell transplant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (estimated)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- Jazz Pharmaceuticals, Deutsche Krebshilfe e.V., Bonn (Germany)
- Study start
- Dec 2005
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 9 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prophylaxis Arm | Experimental | Drug: Defibrotide |
| Control Arm | Active comparator | Drug: Defibrotide |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Age <18 years
- myeloablative conditioning and autologous or allogeneic stem cell transplantation with at least one of the following risk factors for VOD:
Key exclusion criteria (2 listed)
- Pregnant patients
- Patients who are transplanted but do not fulfill any of the above mentioned criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DefibrotideDefibrotide 25 mg/kg/d | Drug | Control Arm, Prophylaxis Arm |
| DefibrotideDefibrotide 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. | Drug | Prophylaxis Arm |
| DefibrotideDefibrotide 25 mg/kg/d iv therapeutically when patients fulfil modified Seattle criteria | Drug | Control Arm |
Primary outcome
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD
Time frame: Day + 30 post HSCT
1 secondary outcome
Occurrence of Multi-System Organ Failure and Survival (all causes of mortality)
Time frame: day +100 post HSCT
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2011.
- Derived from this study: PubMed 37231094Corbacioglu S, Grupp SA, Richardson PG, Duarte R, Pagliuca A, Ruutu T, Mahadeo K, Carreras E. Prevention of veno-occlusive disease/sinusoidal obstruction syndrome: a never-ending story and no easy answer. Bone Marrow Transplant. 2023 Aug;58(8):839-841. doi: 10.1038/s41409-023-02007-2. Epub 2023 May 25. No abstract available.
- Derived from this study: PubMed 22364685Corbacioglu 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.
- sponsor's Web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Selim Corbacioglu, MD principal investigator
University of Ulm, Germany
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Defibrotide in people with Hepatic Veno-Occlusive Disease, run by European Society for Blood and Marrow Transplantation at 30 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Germany, Sweden, Switzerland, Italy, Austria and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to evaluate if prophylactic DF has an impact on the incidence of VOD (time frame: Day + 30 post HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00272948, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2011.