5-day Defibrotide Treatment for Hepatic SOS/VOD

NCT ID: NCT04313036

Last Updated: 2021-04-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-11
• Study Completion Date: 2022-08-01

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Defibrotide

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.

Group Type: EXPERIMENTAL

Defibrotide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Hagen, Patrick A

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick A Hagen, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Patrick A Hagen, MD, MPH

Role: CONTACT

patrick.hagen@lumc.edu

708-327-3157

Mary Lee

Role: CONTACT

mlee@luc.edu

708-327-2241

Facility Contacts

Patrick A Hagen, MD

Role: primary

patrick.hagen@lumc.edu

708-327-3157

Mary Lee, RN

Role: backup

mlee@luc.edu

708-327-2241

Other Identifiers

212665

Identifier Type: -

Identifier Source: org_study_id