Clinical Trial: Study of Panobinostat (LBH589) in Patients With Sickle Cell Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Study to Determine the Safety and Tolerability of Escalating Doses of Panobinostat (LBH589) in Patients With Sickle Cell Disease

Brief 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.

Detailed Summary:

This is a one-arm, open-label, multi-center, 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 Follow-up.Screening Subjects will be screened for eligibility within 28 days of baseline visit (Day 1). Screening assessments will include informed consent, physical exam, vital signs (height, weight, blood pressure, heart rate, height, weight, and respirations), review of medical history, review of concomitant medications, 12-lead electrocardiogram (ECG), echocardiogram, and laboratory assessments. Screening laboratory assessments will include the following: CBC with differential, reticulocytes, complete chemistry panel, LDH, serum ferritin, thyroid function testing, Hb F percentage, F-cells, HIV, urinalysis (with microscopic evaluation if indicated), and serum pregnancy in all females of childbearing potential. Approximately 15 ml (1 tablespoon) of blood will be collected at the screening visit.

Treatment The treatment phase is twelve weeks in duration. Each subject will be assigned to a specified dose level and dosing schedule and will remain with the assigned regimen, if tolerated, throughout the twelve week period. Regardless of specific dosing assignment, all subjects will take study drug thrice weekly (Monday, Wednesday, and Friday). The first three patients to enroll in the study will be assigned to dose level 1 (1
Sponsor: Abdullah Kutlar

Current Primary Outcome: Primary Outcome Measure [ Time Frame: Days 1, 5, 8, 15, 22, 29, 43, 57, 85, 113 ]

To determine the safety and dose limiting toxicities of escalating doses of oral panobinostat in sickle cell disease


Original Primary Outcome: Primary Outcome Measure [ Time Frame: Days 1,5,7,14,21,28,42,56,84, 112 ]

To determine the safety and dose limiting toxicities of escalating doses of oral panobinostat in sickle cell disease


Current Secondary Outcome:

  • Secondary Outcome Measure [ Time Frame: Days 1, 5, 8, 15, 22, 29, 43, 53, 85, 113 ]

    To determine the effect of escalating doses of oral panobinostat on the following parameters:

    I.Overall HbF percentage and F cells

    II. Change in total hemoglobin

    III. Rate of change of total hemoglobin

    IV. Effect on serum inflammation markers and cytokines

  • Exploratory Outcome Measure [ Time Frame: Day 1 and Day 85 ]

    I. Histon acetylation of gamma genes

    II. Methylation of gamma genes



Original Secondary Outcome:

  • Secondary Outcome Measure [ Time Frame: Days 1, 5,7,14, 21,28, 42, 56, 84, 112 ]

    To determine the effect of escalating doses of oral panobinostat on the following parameters:

    I.Overall HbF percentage and F cells

    II. Change in total hemoglobin

    III. Rate of change of total hemoglobin

    IV. Effect on serum inflammation markers and cytokines

  • Exploratory Outcome Measure [ Time Frame: Day 1 and Day 84 ]

    I. Histon acetylation of gamma genes

    II. Methylation of gamma genes



Information By: Augusta University

Dates:
Date Received: November 19, 2010
Date Started: November 2010
Date Completion: December 2019
Last Updated: June 21, 2016
Last Verified: June 2016