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

NCT01245179 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CLBH589BUS43T
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

sickle cell anemia; sickle cell thalassemia; HDAC inhibitor; hemoglobin F; sickle beta thalassemia; Fetal Hemoglobin

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

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

  Days 1, 8, 15, 22, 29, 43, 57, 85, 113

Secondary Outcomes (2)

• Secondary Outcome Measure

  Days 1, 8, 15, 22, 29, 43, 53, 85, 113

• Define mechanisms of effect of panobinostat (Hb F induction and anti-inflammatory effects) and discover biomarkers of treatment response

  Day 1 and Day 85

Study Arms (1)

Panobinostat

EXPERIMENTAL

All patients will receive Panobinostat at specified dose levels and dosing schedules.

Drug: panobinostat

Interventions

panobinostat DRUG

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

Also known as: LBH589, LBH589 lactate, FARYDAK®

Panobinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients who have had a vaso-occlusive crisis within the past 2 weeks that required treatment with parenteral medication.
• Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patients on a chronic transfusion regimen, or any patient who has Hb A% \> 20% from a recent transfusion
• Any of the following laboratory abnormalities derived from the screening visit:
• Absolute neutrophil count (ANC) \< 1.5 x 109/L
• Hemoglobin \< 6 g/dl
• Platelets \< 100x 109/L
• Serum creatinine \>1.5 x Upper limits of normal (ULN)
• AST and ALT \> 2.5 x ULN
• Serum total bilirubin \> 10 mg/dL
• Serum direct bilirubin \> 1 mg/dL
• Albumin \<3.0 g/dl
• Serum potassium \< Lower limits of normal (LLN)
• Total serum calcium \[corrected for serum albumin\] or ionized calcium \<LLN
• Serum magnesium \< LLN

Sponsors & Collaborators

• Abdullah Kutlar: lead
• Secura Bio, Inc.: collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Abdullah Kutlar, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Director of Augusta University Sickle Cell Center

Study Record Dates

• First Submitted: November 19, 2010
• First Posted: November 22, 2010
• Study Start: November 1, 2010
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)