Clinical Trial: A Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Phase II Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease

Brief Summary:

There is a clear need for effective, steroid-sparing agents for the management of chronic graft-versus-host disease (GVHD). Thus, agents like Histone deacetylase (HDAC) inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting graft-versus-leukemia (GVL), may have a central role in the prevention and treatment of GVHD.

This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.


Detailed Summary:

Chronic GVHD is an autoimmune, inflammatory disorder that occurs in the majority of patients who experience acute GVHD. Long-term corticosteroids are still standard therapy for chronic GVHD. Corticosteroids are associated with high morbidity and non-relapse mortality. In addition, corticosteroids are broadly immunosuppressive and can also decrease the GVL effect and increase the incidence of relapse. There is a clear need for effective, steroid-sparing agents for the management of chronic GVHD. Thus, agents like HDAC inhibitors, with the potential of decreasing pro-inflammatory events leading to GVHD without affecting GVL, may have a central role in the prevention and treatment of GVHD.

This study will look at the efficacy of panobinostat (LBH589), an HDAC inhibitor, in the treatment of patients with chronic GVHD who have failed corticosteroids. In this group of patients, effective steroid-sparing options are limited and are usually associated with profound immunosuppression and decreased GVL effect.


Sponsor: SCRI Development Innovations, LLC

Current Primary Outcome: To assess the response rate to panobinostat of patients with cGvHD inadequately treated with steroids and calcineurin inhibitors. [ Time Frame: 30 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • To evaluate the safety and tolerability of panobinostat in patients with cGvHD. [ Time Frame: 30 months ]
  • To assess the steroid-sparing capacity of panobinostat (as proportion of patients able to discontinue steroids while receiving, or following therapy with, panobinostat). [ Time Frame: 30 months ]
  • To assess changes in quality of life (QOL) after treatment with panobinostat. [ Time Frame: 30 months ]
  • To analyze survival at 6 and 12 months after initiation of panobinostat. [ Time Frame: 30 months ]
  • To evaluate the relapse rate of the underlying malignancy as well as the occurrence of second malignancies at 6 and 12 months after initiation of panobinostat. [ Time Frame: 30 months ]


Original Secondary Outcome: Same as current

Information By: SCRI Development Innovations, LLC

Dates:
Date Received: December 7, 2009
Date Started:
Date Completion:
Last Updated: February 11, 2013
Last Verified: February 2013