Sertraline in Treatment of Low-Risk Myelodysplastic Syndrome

This pilot study investigates clinical benefit of four 28-day cycles of sertraline in
low-risk MDS patients. Participants will receive 100mg of oral sertraline daily. The study
will also evaluate potential associated biological mechanisms of action.

Inclusion Criteria:

- Diagnosis of Very Low or Low risk MDS defined by IPSS-R confirmed by a bone marrow
aspirate and biopsy (Blast count must be < 20%)

- Hemoglobin < 11 g/dL, or transfusion dependency.

- Platelet count <100,000/mm3

- Absolute Neutrophil Count (ANC) < 1000/mm3

- Life expectancy of 12 months or greater

- ECOG Performance status of 0 - 3

- Age ≥ 18 years

- Willing to use medically acceptable methods of birth control during the study and for
28 days after discontinuing study treatment

- All subjects must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines

- Both men and women and members of all races and ethnic groups

Exclusion Criteria:

- Previous exposure to 5-AC (azacitidine) or decitabine

- Use of antidepressants such as sertraline within 6 weeks OR use of paroxetine,
fluoxetine, or citalopram within 3 months prior to registration

- Active cases (within past 12 months) of depressive disorder, manic episodes, and/or
anxiety requiring active treatment with an SSRI. Patients being treated with an SSRI
for non-psychiatric indication are allowed, and should go through the appropriate
washout.

- Previous or concurrent malignancy, except treated basal cell or squamous cell cancer
of skin, treated in situ cervical cancer, treated lobular or ductal carcinoma in situ
in one breast, or any other cancer for which the patient has been disease-free for at
least 5 years

- Actively receiving chemo-immunotherapy

- Evidence of active infection

- Treatment with steroids or immunosuppressive therapy such as cyclosporine, tacrolimus,
anti-thymocyte globulin (ATG) within 6 months of registration

- Platelet transfusion within 8 weeks of registration.

- Platelet count < 20,000/mm3 within 14 days of registration.

- Active treatment with growth factors such erythropoietin stimulating agent (ESA),
granulocyte colony-stimulating factor (GCSF), thrombopoietin stimulating factor within
8 weeks of registration

- Treatment with an investigational agent within 4 weeks of registration

- History of autoimmune disease including rheumatoid arthritis, systemic lupus and
sarcoidosis

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sertraline

- Known history of splenomegaly

- Pregnant or nursing women are excluded from this study because Sertraline is a Class C
agent with the potential for teratogenic or abortive effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with sertraline, breast feeding should be discontinued.

- HIV: Given high risk for Immune thrombocytopenic purpura, HIV associated neutropenia
and combination antiretroviral therapy, patients with known HIV are excluded because
of the potential for pharmacokinetic interactions with sertraline.

- Any condition or illness that, in the Investigator's opinion, would place the subject
at unacceptable risk if he/she were to participate.