Pyrimethamine for Intermediate/High-risk Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

Participants at or above the age of 18 years
Diagnosis of MDS confirmed within 6 months, by review of patient chart, prior to study entry according to WHO (World Health Organization) criteria or FAB (French-American-British) classification
MDS classified as intermediate-1, intermediate-2 or high risk as per the International Prognostic Scoring System-Revised (IPSS-R) score with a confirmed diagnosis of MDS with cytogenetic abnormalities at diagnosis and bone marrow blast percentage between 10 and 30 percent (for patients with cytogenetic failure or dry tap)

Potential participants must meet ONE of the following:

Progression (according to 2006 International Working Group (IWG) criteria) at any time after initiation of azacitidine or decitabine treatment during the past 3 years; OR
Failure to achieve complete or partial response or hematological improvement (according to 2006 IWG) after at least four cycles of azacitidine or decitabine administered during the past 3 years OR
Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria) observed after at least four cycles of azacitidine or decitabine administered during the past 3 years OR
Intolerance to azacitidine or decitabine defined by drug-related more than or equal to Grade 3 liver or renal toxicity leading to treatment discontinuation during the past 3 years
Off all other treatments for MDS for at least 3 weeks. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Willing to adhere to the prohibitions and restrictions specified in this protocol
Patient (or patient's legally authorized representative) must signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
Adequate organ and marrow function as defined in the protocol.
Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

Exclusion Criteria:

Current or anticipated use of other investigational agents
Participants who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from clinically significant adverse events due to agents administered more than 3 weeks earlier.
History of allergic reactions or sensitivity to pyrimethamine
Patients with a history of folic acid deficiency, currently on folic acid replacement therapy or a previous history of megaloblastic anemia thought related to folic acid deficiency
Current use or anticipated need for treatment with any medications or substances that are inhibitors or inducers of CYP2C9.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or nursing women