Clinical Trial: European VOD Registry

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: A Multi-centre, Multinational, Prospective Observational Registry to Collect Safety and Outcome Data in Patients Diagnosed With Severe Hepatic VOD Following Hematopoietic Stem Cell Transplantation (HS

Brief Summary:

Following the licencing of a new drug, Defitelio®, indicated for the treatment of severe Veno-Occlusive Disease of the liver (sVOD), a rare but serious complication of haematopoietic stem cell transplantation (HSCT), the pharmaceutical company that manufactures Defitelio® (Gentium, a Jazz Pharmaceuticals Company) - as a specific obligation (SOB) - has been required by PRAC to set up a disease registry to collect safety and outcome data, and to assess patterns of utilization of Defitelio® in the post-approval setting. This registry is a Post Authorization Safety Study (PASS), which is being coordinated through the European Society for Blood and Marrow Transplantation (EBMT). Following appropriate consent, data from patients who undergo haematopoietic stem cell transplantation are routinely collected at the local centre for the EBMT database. For this study, the sites are being asked to collect additional anonymised clinical data from patients who develop this complication or who have been treated with Defitelio® for other reasons than sVOD. The study simply requires collection of data which is already recorded in the patient charts, but not routinely collected.

The study DOES NOT involve decisions about treatment, which are clinical decisions, but merely collection of data for patients who develop this complication, whether or not they receive treatment and for patients who are treated with Defitelio® for any other reasons.


Detailed Summary:

Defitelio® has been granted a Marketing Authorisation in Europe under exceptional circumstances. Defitelio® is indicated for the treatment of severe hepatic Veno-Occlusive Disease (sVOD) also known as sinusoidal obstruction syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.

It is indicated in adults and in adolescents, children and infants over 1 month of age.

As a specific obligation (SOB), Gentium has been required to set up a disease registry to collect safety and outcome data, and to assess patterns of utilization of Defitelio® in the post-approval setting.

This is a multi-centre, multinational and prospective observational disease registry of patients with severe hepatic VOD following HSCT, to record patients treated with Defitelio® or supportive care.

Gentium has been required to ensure that information regarding all potential and identified risks reported in the most recent version of the Risk Management Plan is being collected.

Hepatic VOD is one of the most common life-threatening regimen-related toxicities that constitutes a barrier to successful allogeneic and autologous HSCT. VOD is characterised by rapid weight gain, painful hepatomegaly, hyperbilirubinemia/jaundice, and ascites/fluid retention, without other identifiable causes for liver disease (Richardson, 2012). In a recent survey on 135 studies performed between 1997 and October 2007, the overall mean incidence of VOD has been reported to be 13.7% with a lower rate of 9.6% when Baltimore criteria were applied (Coppell, 2010).

The severe form of the disease, usually associated with pulmonary dysfunction and/or renal
Sponsor: European Group for Blood and Marrow Transplantation

Current Primary Outcome: Incidence rate of specific SAE of interest [ Time Frame: over 12 months ]

Assess the incidence rate of specific SAEs of interest (including fatalities) in patients with severe hepatic VOD treated with Defitelio® and to compare these rates with those occurring in a similar population not treated with Defitelio®.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Describe the population [ Time Frame: Enrolment ]
    To describe the population treated with Defitelio® and controls (age, gender, ethnicity, patients with pre-existing liver or severe renal insufficiency; patient with intrinsic lung disease)
  • GvHD incidence [ Time Frame: over 12 months ]
    Determine the incidence rate of Graft versus host disease (GvHD) in adult and paediatric patients receiving Defitelio® and in controls
  • Survival [ Time Frame: over 12 months ]
    To determine survival by Day+100 post-HSCT, overall mortality and mortality due to VOD in patients treated with Defitelio® and in controls
  • VOD/MOF Resolution [ Time Frame: over 12 months ]
    To determine the rate of Veno Occlusive Disease/Multi Organ Failure resolution any time after treatment initiation in patients treated with Defitelio® and in controls.


Original Secondary Outcome: Same as current

Information By: European Group for Blood and Marrow Transplantation

Dates:
Date Received: January 24, 2017
Date Started: April 2015
Date Completion: December 2018
Last Updated: January 24, 2017
Last Verified: January 2017