Study of Decitabine and Tetrahydrouridine (THU) in Patients With Sickle Cell Disease

Exclusion Criteria

• •Inability to give informed consent.
• •Experienced severe sepsis or septic shock within the previous 12 weeks.
• •Last HU dose was ingested within the previous 4 weeks.
• •Currently pregnant or breast-feeding.
• •Alanine aminotransferase (ALT) greater than or equal to two times (2X) the upper limit of normal or albumin \<2.0 mg/dL or direct (conjugated) bilirubin greater than or equal to 1.5 mg/dl.
• •Serum creatinine \>2.9 mg/dL and calculated creatinine clearance \<30 mL/min.
• •Platelet count \>800 x 109/L.
• •Absolute neutrophil count \<1.5 x 109/L.
• •Female of active childbearing potential who is unwilling to use at least one of the two following forms of birth control:
• •(i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of THU-decitabine OR (ii) intrauterine device (IUD).
• •Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of THU-decitabine. This requirement applies also to males who have had a successful vasectomy.
• •Altered mental status or recurrent seizures requiring anti-seizure medications.
• •Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
• •Concurrent diagnosis of malignancy including myelodysplastic syndromes (MDS), leukemia, or an abnormal karyotype.
• •Vitamin-B12, folate, or iron deficient (until corrected).
• •New York Heart Association (NYHA) class III/IV status.
• •Eastern Co-operative Oncology Group (ECOG) performance status greater than or equal to 3.
• •Participant is on chronic transfusion therapy (e.g., for history of Transient Ischemic Attack (TIA) or stroke) and medically contraindicated to discontinue transfusions (unless multiple allo-antibodies prevent the patient from getting transfusions as scheduled).
• •Known history of illicit drug or alcohol abuse within the past 12 months.
• •Other experimental or investigational drug therapy in the past 28 days.