5-day Defibrotide Treatment for Hepatic SOS/VOD

Loyola University

Status and phase: Unknown; Phase 2

Conditions: Bone Marrow Transplant Complications; Sinusoidal Obstruction Syndrome; Veno-occlusive Disease

Treatments: Drug: Defibrotide

Study type: Interventional

Funder types: Other

Identifiers

NCT04313036

212665

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Defibrotide

Experimental group

Description:

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.

Treatment:

Drug: Defibrotide