Sinusoidal Obstruction SyndromePhase 2NCT04313036
5-day Defibrotide Treatment for Hepatic SOS/VOD
A Phase 2 study testing Defibrotide in people with Sinusoidal Obstruction Syndrome and Veno-occlusive Disease, run by Loyola University at 1 site in United States.
Trial summary
Sinusoidal Obstruction Syndrome (SOS), also referred to as hepatic veno-occlusive disease (VOD), is rare but serious complication of allogeneic stem cell transplantation (allo-SCT). Defibrotide is the only FDA approved therapy to treat SOS and has significantly improved outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sinusoidal Obstruction Syndrome, Veno-occlusive Disease, Bone Marrow Transplant Complications
- 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
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2021to 1 Aug 2022
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who underwent allogeneic stem cell transplantation
- Age >/= 18 years
- Diagnosed hepatic SOS/VOD either by Baltimore Criteria or Modified Seattle Criteria including up to 60 days post-transplantation.
Who cannot join
- Significant uncontrolled bleeding
- Prior or concurrent systemic t-PA
- Concomitant use of therapeutic heparin or other anticoagulants (except use of heparin for central access patency)
- Hemodynamic instability (>1 pressor gent to maintain blood pressure)
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Patrick A Hagen, MD, 708-327-3157, patrick.hagen@lumc.edu
Mary Lee, RN, 708-327-2241, mlee@luc.edu
About this study
Official title: Phase II Open Label Study to Assess Efficacy of 5-day Defibrotide Treatment for Hepatic SOS/VOD
Sinusoidal Obstruction Syndrome (SOS), also referred to as hepatic veno-occlusive disease (VOD), is rare but serious complication of allogeneic stem cell transplantation (allo-SCT). Defibrotide is the only FDA approved therapy to treat SOS and has significantly improved outcomes. When applied early, SOS symptoms often quickly improve and an abbreviated course can be applied. This study is looking at an abbreviated 5 day course of defibrotide in those patients with a complete response to therapy with the primary outcome being day 100 overall survival as compared to history data.
Read the detailed description
Sinusoidal obstructive syndrome (SOS) has a reported mean incidence of 13.7% and even among those undergoing reduced intensity conditioning regimens is approximately 9%. SOS is a clinical syndrome characterized by painful hepatomegaly, jaundice, ascites, fluid retention, and weight gain. The onset is usually before day 35 after stem cell infusion. SOS ranges in severity from a mild reversible disease to a severe syndrome associated with multiorgan failure (MOF) and death. Prior to the introduction of defibrotide, severe SOS was nearly universally fatal with a mortality rate approaching 100% by day 100 after allo-SCT.
The diagnosis of SOS/VOD is clinical and should be considered in any patient who has undergone hematopoietic stem cell transplantation and develops liver dysfunction. Patients with mild or moderate disease have reasonably good outcomes with supportive therapy alone while in contrast prognosis is much worse in severe SOS which occurs in about 25-30% cases.
Defibrotide is the only established Food and Drug Administration (FDA) approved therapy to treat SOS. It is now approved for use in adults and children with SOS with renal or pulmonary dysfunction following HCT. The standard treatment is 25 mg/kg/day in 4 divided doses of 6.25 mg/kg for 21 days. However, responses are frequently brisk and complete in many patients thus it has been postulated that in responding patients this treatment course could be abbreviated given the risk for adverse events such as hypotension/shock and hemorrhage.
This is an open label pilot study evaluating an abbreviated 5 (as compared to 21) day course of defibrotide in patients with confirmed SOS. The primary outcome is day 100 survival as compared to historical data.
- Conditions
- Sinusoidal Obstruction Syndrome, Veno-occlusive Disease, Bone Marrow Transplant Complications
- Being tested
- Defibrotide
- Keywords
- defibrotide, Sinusoidal, Veno-occlusive, Bone Marrow Transplant, allogeneic 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
25 mg/kg/day at 4 divided doses of 6.25 mg/kg, 2-h infusion given for 5 days, if not in CR treatment continued for >/= 21 days or per discretion of enrolling physician.
| Study group | Role | What they receive |
|---|---|---|
| Defibrotide | Experimental | 5 day course of defibrotide at standard dosing 25 mg/kg/day in 4 divided doses of 6.25 mg/kg. If not in CR by day 5, will be given for >/= 21 days or per discretion of enrolling physician. Receives: Drug: Defibrotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 100 overall survival
Assess day 100 survival of 5-day defibrotide treatment for hepatic SOS/VOD in allogeneic stem cell transplant patients compared to standard 21-day treatment in the reported literature.
Measured: 100 days
Secondary outcomes (3)
Complete response day 100
Assess complete response (CR) rates for hepatic SOS/VOD by day +100 defined as resolution of parameters used to document SOS/VOD.
Measured: 100 days
Complete response day 5
Assess complete response (CR) rates for hepatic SOS/VOD by day +5 as defined by resolution of parameters used to document SOS/VOD.
Measured: 5 days
Complete response day 30
Assess complete response (CR) rates for hepatic SOS/VOD by day +30 as defined by resolution of parameters used to document SOS/VOD.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2020
- Study start11 Mar 2021
- Primary completion1 May 2022 (estimated)
- Study completion1 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sinusoidal Obstruction SyndromeStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The goal of this study is to assess the 100-day survival of a 5-day defibrotide treatment for hepatic SOS in allogeneic stem cell transplant patients compared to the standard 21-day treatment. It is hypothesized that the 5-day treatment will have non-inferior 100-day survival rates to the 21-day treatment. Historically, 100-day survival has been 58.9% in moderate and 38.2% in severe SOS. Investigators believe that the null survival for the 21-day defibrotide treatment is 50%. Investigators wish to determine non-inferiority of the 5-day treatment with a 5% margin of error.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hagen, Patrick A, Loyola University
- Investigators
- Patrick A Hagen, MD, Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04313036
- Sponsor's protocol ID
- 212665
- Status last verified
- Apr 2021
- First submitted
- 16 Mar 2020
- Last updated
- 23 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open Label Study to Assess Efficacy of 5-day Defibrotide Treatment for Hepatic SOS/VOD
- ClinicalTrials.gov ID
- NCT04313036
- Acronym / sponsor ID
- 212665
- Conditions
- Sinusoidal Obstruction Syndrome, Veno-occlusive Disease, Bone Marrow Transplant Complications
- Keywords
- defibrotide, Sinusoidal, Veno-occlusive, Bone Marrow Transplant, allogeneic stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Study start
- 11 Mar 2021 (actual)
- Primary completion
- 1 May 2022 (estimated)
- Study completion
- 1 Aug 2022 (estimated)
- First posted
- 18 Mar 2020 (actual)
- 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.
Sinusoidal Obstruction Syndrome (SOS), also referred to as hepatic veno-occlusive disease (VOD), is rare but serious complication of allogeneic stem cell transplantation (allo-SCT). Defibrotide is the only FDA approved therapy to treat SOS and has significantly improved outcomes. When applied early, SOS symptoms often quickly improve and an abbreviated course can be applied. This study is looking at an abbreviated 5 day course of defibrotide in those patients with a complete response to therapy with the primary outcome being day 100 overall survival as compared to history data.
Detailed description
Sinusoidal obstructive syndrome (SOS) has a reported mean incidence of 13.7% and even among those undergoing reduced intensity conditioning regimens is approximately 9%. SOS is a clinical syndrome characterized by painful hepatomegaly, jaundice, ascites, fluid retention, and weight gain. The onset is usually before day 35 after stem cell infusion. SOS ranges in severity from a mild reversible disease to a severe syndrome associated with multiorgan failure (MOF) and death. Prior to the introduction of defibrotide, severe SOS was nearly universally fatal with a mortality rate approaching 100% by day 100 after allo-SCT.
The diagnosis of SOS/VOD is clinical and should be considered in any patient who has undergone hematopoietic stem cell transplantation and develops liver dysfunction. Patients with mild or moderate disease have reasonably good outcomes with supportive therapy alone while in contrast prognosis is much worse in severe SOS which occurs in about 25-30% cases.
Defibrotide is the only established Food and Drug Administration (FDA) approved therapy to treat SOS. It is now approved for use in adults and children with SOS with renal or pulmonary dysfunction following HCT. The standard treatment is 25 mg/kg/day in 4 divided doses of 6.25 mg/kg for 21 days. However, responses are frequently brisk and complete in many patients thus it has been postulated that in responding patients this treatment course could be abbreviated given the risk for adverse events such as hypotension/shock and hemorrhage.
This is an open label pilot study evaluating an abbreviated 5 (as compared to 21) day course of defibrotide in patients with confirmed SOS. The primary outcome is day 100 survival as compared to historical data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The goal of this study is to assess the 100-day survival of a 5-day defibrotide treatment for hepatic SOS in allogeneic stem cell transplant patients compared to the standard 21-day treatment. It is hypothesized that the 5-day treatment will have non-inferior 100-day survival rates to the 21-day treatment. Historically, 100-day survival has been 58.9% in moderate and 38.2% in severe SOS. Investigators believe that the null survival for the 21-day defibrotide treatment is 50%. Investigators wish to determine non-inferiority of the 5-day treatment with a 5% margin of error.
| Arm | Type | Receives |
|---|---|---|
| Defibrotide | Experimental | Drug: Defibrotide5 day course of defibrotide at standard dosing 25 mg/kg/day in 4 divided doses of 6.25 mg/kg. If not in CR by day 5, will be given for >/= 21 days or per discretion of enrolling physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients who underwent allogeneic stem cell transplantation
- Age >/= 18 years
- Diagnosed hepatic SOS/VOD either by Baltimore Criteria or Modified Seattle Criteria including up to 60 days post-transplantation.
Key exclusion criteria (4 listed)
- Significant uncontrolled bleeding
- Prior or concurrent systemic t-PA
- Concomitant use of therapeutic heparin or other anticoagulants (except use of heparin for central access patency)
- Hemodynamic instability (>1 pressor gent to maintain blood pressure)
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 |
|---|---|---|
| Defibrotide25 mg/kg/day at 4 divided doses of 6.25 mg/kg, 2-h infusion given for 5 days, if not in CR treatment continued for >/= 21 days or per discretion of enrolling physician. | Drug | Defibrotide |
Primary outcome
Day 100 overall survival
Time frame: 100 days
Assess day 100 survival of 5-day defibrotide treatment for hepatic SOS/VOD in allogeneic stem cell transplant patients compared to standard 21-day treatment in the reported literature.
3 secondary outcomes
Complete response day 100
Time frame: 100 days
Complete response day 5
Time frame: 5 days
Complete response day 30
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
- Individual participant dataSharing planned: No
Related trials for Sinusoidal Obstruction Syndrome
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingObservational study
A Prospective Registry of Pediatric Cellular Therapy Patients at Risk for Endothelial Dysfunction, Sinusoidal Obstruction Syndrome and/or Multi-Organ Dysfunction Syndrome (MODS).
Hematopoietic Cell Transplantation
RecruitingPhase 2
Defibrotide Dose-escalation for SOS Post-HSCT
Sinusoidal Obstruction Syndrome, Veno-occlusive Disease
RecruitingObservational study
Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation
GVHD - Graft-Versus-Host Disease, Infections After HSCT
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.
Patrick A Hagen, MD principal investigator
Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Defibrotide in people with Sinusoidal Obstruction Syndrome and Veno-occlusive Disease, run by Loyola University at 1 site in United States.
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 3 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrick A Hagen, MD, MPH (708-327-3157, patrick.hagen@lumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Day 100 overall survival (time frame: 100 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2021.