Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease
To test a new agent, LBH589, in combination with glucocorticoids as initial therapy of acute graft versus host disease (GVHD).
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial Evaluating the Use of Histone Deacetylase Inhibitor LBH589 in Addition to Corticosteroids in Patients With Acute Graft Versus Host Disease|
- Safety of LBH589 (Phase I) [ Time Frame: 36 +/- 3 days from initiation of LBH589 ] [ Designated as safety issue: Yes ]LBH589 treatment safety will be determined by the proportion of study patients who develop adverse events ≥ grade 3 severity as graded by Common Terminology Criteria for Adverse Events (CTCAE Version 4.0)
- Efficacy of LBH589 (Phase II) [ Time Frame: 36 +/- 3 days from initiation of LBH589 ] [ Designated as safety issue: Yes ]Efficacy endpoint will be carried out based on patient response rate of complete remission. Assessment of GVHD will include the skin, liver and gut. Other possible etiologies of organ disease such as C difficile enterocolitis, viral infection, drug reaction, veno-occlusive disease of the liver, etc., will be excluded by appropriate tests.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Experimental: LBH589, in Addition to Glucocorticoids
Phase I Dose Escalation, Followed by Phase II Treatment at Maximum Tolerated Dose (MTD) of LBH589, in Addition to Glucocorticoids.
Drug: Panobinostat (LBH589)
Phase I, dose escalation levels for LBH589; patients treated with LBH589 PO three times a week (48 hours apart) every week for four weeks.
DL -1* 5 mg PO;
DL 1 10 mg PO (starting dose level);
DL 2 15 mg PO;
DL 3 20 mg PO;
DL 4 25 mg PO ;
*DL -1, represents a potential treatment dose for patients requiring a dose reduction from a higher dose level. In addition, dose level -1 may be used as a contingency dose level if the starting dose level of LBH589 is not tolerated in the initial cohort.
Phase II, patients treated with LBH589 PO (MTD to be determined) three times a week (48 hours apart) every week for four weeks
Dose escalation study to test the safety (Phase I), pharmacology and preliminary clinical activity (Phase II) of a Novel histone deacetylase (HDAC) inhibitor, LBH589, in the treatment of the following GVHD presentations: Classic, Late-onset acute GVHD, Recurrent acute GVHD, Overlap syndrome.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111526
|United States, Florida|
|H Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Lia Perez, MD||H. Lee Moffitt Cancer Center and Research Institute|