5-day Defibrotide Treatment for Hepatic SOS/VOD

Bone Marrow Transplant Complications Clinical Trial

Official title:

Phase II Open Label Study to Assess Efficacy of 5-day Defibrotide Treatment for Hepatic SOS/VOD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04313036
• Other study ID #: 212665
• Status: Recruiting
• Phase: Phase 2
• Start date: March 11, 2021
• Est. completion date: August 1, 2022

Study information

• Verified date: April 2021
• Source: Loyola University
• Contact: Patrick A Hagen, MD, MPH
• Phone: 708-327-3157
• Email: patrick.hagen[@]lumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 1, 2022
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients who underwent allogeneic stem cell transplantation

2. Age >/= 18 years

3. Diagnosed hepatic SOS/VOD either by Baltimore Criteria or Modified Seattle Criteria including up to 60 days post-transplantation.

Exclusion Criteria:

1. Significant uncontrolled bleeding

2. Prior or concurrent systemic t-PA

3. Concomitant use of therapeutic heparin or other anticoagulants (except use of heparin for central access patency)

4. Hemodynamic instability (>1 pressor gent to maintain blood pressure)

Related Conditions & MeSH terms

• Bone Marrow Transplant Complications
• Hepatic Veno-Occlusive Disease
• Sinusoidal Obstruction Syndrome
• Veno-occlusive Disease

Intervention

Drug:
• Defibrotide
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.

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Loyola University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	100 days
Secondary	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.	100 days
Secondary	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.	5 days
Secondary	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.	30 days