A Study of Oral Tetrahydrouridine-Decitabine in Relapsed or Refractory Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

• Patients must have a diagnosis of MDS that has received one or more prior standardtherapies and is relapsed or refractory

• Patients must be 18 years of age or older

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof ≤ 3

• Patients must have adequate end-organ function

• Patient's body weight must be ≥ 41 kg

• Subjects must be able to understand and willing to sign a written informed consentdocument and complete study-related procedures.

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL)

• Prior treatment with ≥4 28-day cycles of parenteral or oral decitabine

• No other disease-directed therapy, save for hydroxyurea, including experimental orinvestigational drug therapy for 14 days prior to study entry (hydroxyurea should bediscontinued ≥24 hours prior to initiation of study drug)

• Requiring concomitant treatment with drugs that are cytidine deaminase (CDA)substrates and/or inhibitors, e.g., cytarabine, 5-azacytidine, gemcitabine

• Currently pregnant or breastfeeding. Females of childbearing potential must have anegative serum pregnancy test within 72 hours of treatment start.

• Uncontrolled intercurrent illness that could limit life expectancy or ability tocomplete study correlates

• Women of Childbearing Potential (WOCBP) who are unwilling to agree to use dualcontraceptive measures (i.e., hormonal or barrier method of birth control;abstinence, condom) prior to study entry, for the duration of study participation,and until 6 months after taking the last dose of THU/decitabine

• Sexually active male who is unwilling to use a condom when engaging in any sexualcontact with a WOCBP, beginning at the screening visit and continuing until 6 monthsafter taking the last dose of THU/decitabine

• 9. Patients with uncontrolled active human retrovirus (HIV) infection, as this willfurther increase the risk for opportunistic infections. However, patients with HIVwith undetectable viral load by polymerase chain reaction (PCR), withoutopportunistic infection, and on a stable regimen of antiretroviral therapy areeligible