Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease

Inclusion Criteria:

• Diagnosis of sickle cell disease
• Clinically significant disease defined as at least 1 painful episode per year averaged over the previous 3 years or a history of priapism, stroke, acute chest syndrome, avascular necrosis, multi-organ failure or the need for chronic narcotic medications for pain from sickle cell disease
• Must have failed a previous attempt at treatment with hydroxyurea defined as the inability to achieve a significant absolute increase in % fetal hemoglobin or the inability to tolerate hydroxyurea treatment due to severe side effects such as but not limited to myelosuppression, gastrointestinal symptoms, edema or hepatic enzyme elevations or have contraindications to hydroxyurea
• 18 years of age or older
• Hematologic laboratory values as outlined in the protocol
• Non-hematologic laboratory values as outlined in the protocol
• Must agree not to donate blood or other bodily fluid while taking the study drug and for 28 days thereafter
• Women of child-bearing potential (WCBP) must have a negative serum pregnancy test 72 hours or less prior to starting treatment
• Women of child-bearing potential and men must agree to use 2 forms of adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Subjects with hemoglobin SC or SB+ thalassemia
• Subjects on chronic transfusion program
• Subjects who have received RBC transfusions cannot have >15% adult hemoglobin
• Known positive status for HIV, active hepatitis B or hepatitis C
• Pregnant or breast feeding women
• Individuals with a history of malignancy are ineligible except for the following circumstances. Individuals with a history of malignancy are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancer are eligible if diagnosed and adequately treated within the past 5 years: cervical or breast cancer in situ, and basal cell or squamous cell carcinoma of the skin
• Subjects with a history of thrombosis or other reason (other than sickle cell disease) for enhanced thrombotic risk
• Subjects with unresolved infections
• Severe or uncontrolled medical conditions that could compromise study participation
• Subjects on fetal hemoglobin inducing agents
• Subjects on any other experimental treatment within 90 days of the first dose of study drug or who have not recovered from the side effects of such therapy
• Known allergic reaction to a histone deacetylase inhibitor
• Subjects who have received valproic acid for treatment of epilepsy within 30 days of enrollment
• Subjects who have received any HDAC inhibitors other than valproic acid