Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease
Condition: Sickle Cell Disease; Sickle Cell Anemia
MeSH terms: Anemia, Sickle Cell
Intervention: vorinostat
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: fetal hemoglobin; vorinostat; HDAC inhibitor; SAHA

Summary:

      Sickle Cell Disease (SCD) is a hereditary anemia that causes the red blood cells to change
      their shape from a round and doughnut-like shape to a half-moon/crescent, or sickled shape.
      People who have SCD have a different type of hemoglobin (protein that carries oxygen). This
      different type of hemoglobin makes the red blood cells change into a crescent shape under
      certain conditions. Sickle-shaped cells are a problem because they often get stuck in the
      blood vessels blocking the flow of blood and can cause inflammation and injury to important
      areas of the body. All babies are born with hemoglobin called fetal hemoglobin (HbF). Soon
      after birth, HbF production slows down and another hemoglobin called adult hemoglobin (HbA)
      is made. Clinical studies have shown that increasing the amount of HbF in the blood may
      prevent sickling of the red blood cells. Vorinostat has been used in the treatment of cancers
      and in other research studies and information from those suggests that it may help treat SCD
      by increasing the amount of HbF in the blood. The purpose of this research study is to
      determine the effectiveness and safety of vorinostat when used to treat SCD.
    

Eligibility criteria:

        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