Phase I Study to Determine the Safety and Tolerability of Escalating Doses of Panobinostat (LBH589) in Patients With Sickle Cell Disease
Abdullah Kutlar
Summary
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.
Description
This is a one-arm, open-label, Phase I, dose-escalation study of Panobinostat administered via different dosing schedules. In each schedule, this study is designed to determine the MTD (maximum tolerated dose) and DLT (dose limiting toxicities) of panobinostat as a single agent, and to characterize the safety and tolerability of panobinostat in adult patients with sickle cell disease who have failed to respond to hydroxyurea therapy (clinically or hematologically) or are intolerant of or refuse hydroxyurea therapy. The study consists of a Screening Phase, Treatment Phase, and Post-Treatment Fo…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria 1. Male or female patients ages ≥ 18 years 2. Confirmed diagnosis of homozygous SS or S-β0Thalassemia 3. Intolerance to hydroxyurea therapy, refusal of hydroxyurea therapy, or failure to respond (refractoriness) to hydroxyurea therapy, either clinically or hematologically. 4. Clinically significant sickle cell disease as defined by: 1. At least two hospitalizations over the past twelve months for any complication of sickle cell disease; or 2. At least three pain crises over the past twelve months that last four or more hours and require a visit to a medical facility…
Interventions
- Drugpanobinostat
Panobinostat oral capsules taken THRICE WEEKLY (Monday, Wednesday, and Friday) for 12 weeks, exploring the following dosing regimens: 1. 15 mg MWF 3 weeks on, 1 week off (if needed) 2. 15 mg MWF every week (starting dose) 3. 20 mg MWF 3 weeks on, 1 week off 4. 20 mg MWF every week
Location
- Augusta UniversityAugusta, Georgia