Phase I Study to Determine the Safety and Tolerability of Escalating Doses of Panobinostat (LBH589) in Patients With Sickle Cell Disease
The goal of this clinical research study is to find out about the safety and effects of a drug called panobinostat when given to adults with sickle cell disease. Panobinostat is a pan histone deacetylase (HDAC) inhibitor. HDAC inhibitors have been shown to significantly increase hemoglobin F induction, which is well documented to improve outcomes in sickle cell disease. HDAC inhibitors are also known to potently inhibit cell-specific inflammation, which is a primary contributor to the debilitating effects of sickle cell disease. Given the relevance of these mechanisms of action in SCD, panobinostat may prove to contribute significantly to the management of SCD patients, a population in critical need of further effective treatment options.
• Male or female patients ages ≥ 18 years
• Confirmed diagnosis of homozygous SS or S-β0Thalassemia
• Intolerance to hydroxyurea therapy, refusal of hydroxyurea therapy, or failure to respond (refractoriness) to hydroxyurea therapy, either clinically or hematologically.
• Clinically significant sickle cell disease as defined by:
‣ At least two hospitalizations over the past twelve months for any complication of sickle cell disease; or
⁃ At least three pain crises over the past twelve months that last four or more hours and require a visit to a medical facility for treatment with oral or parenteral narcotics; or
⁃ History of recurrent leg ulcers; or
⁃ History of Acute Chest Syndrome within the past five years; or
⁃ History of priapism requiring medical intervention within the past two years; or
⁃ History of stroke (but not currently on a chronic blood transfusion regimen).
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed.
• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.