The purpose of this study is to see if selinexor will improve the blood counts and bone marrow function in people with your type of MDS.

Inclusion Criteria:

• Written informed consent in accordance with federal, local, and institutional guidelines
• Age ≥18 years
• Patients with Myelodysplastic Syndromes refractory (primary or acquired resistance) to hypomethylating agents(decitabine or 5-azacytidine). At least 4 1- month cycles of prior decitabine or SGI-110 OR 6 1-month cycles of 5-azacytidine (IV, subcutaneous, or oral is required unless the patient has progressive disease prior to completing the required number of cycles.
• Histologically confirmed diagnosis of a Myelodysplastic Syndrome, meeting criteria for any subtype in the FAB or WHO classification systems with any IPSS score.
• Patients with MDS who relapse after allogeneic stem cell transplant are eligible if they received standard dose decitabine or 5-azacytidine prior to or after stem cell transplant as defined in inclusion criteria 3.
• If patient has undergone prior allogeneic stem cell transplant, they must be greater than 100 days post transplant and have ≤ grade 2 graft-versus-host disease
• There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Patients receiving erythropoietin (darbepoetin, epoetin alfa) must be on a stable dose and with stable transfusion requirement or hemoglobin level during the 8 weeks prior to study entry.
• Adequate hepatic function within 21 days prior to C1D1: total bilirubin <2 times the upper limit of normal (ULN), asparate aminotransferase (AST) <2.5 times ULN and alanine aminotransferase (ALT) <2.5 times ULN.
• Adequate renal function within 21 days prior to C1D1: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault.
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.

Exclusion Criteria:

• Patients who are pregnant or lactating;
• Chemotherapy or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1. Hydroxyurea may be continued until 72 hours prior to first dose and at least 24 hours before the baseline bone marrow aspiration is performed;
• Major surgery within four weeks before Day 1;
• Unstable cardiovascular function defined as symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (ie: ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), congestive heart failure (CHF) of NYHA Class ≥3, or myocardial infarction (MI) within 3 months;
• Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within one week prior to first dose; Prophylactic antimicrobials are permitted.
• Known to be HIV seropositive;
• Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen);
• Patients with another active malignancy. Asymptomatic sites of disease are not considered active. Treated or untreated sites of disease may be considered inactive if they are stable for at least 2 months and are not expected to require therapy for 4 months.
• Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
• Grade ≥2 peripheral neuropathy at baseline (within 21 days prior to cycle 1 day 1).
• History of seizures, movement disorders or cerebrovascular accident within the past 1 years prior to cycle 1 day 1.
• Patients with macular degeneration with markedly decreased visual acuity, patients with markedly decreased visual acuity (no specific etiology) or uncontrolled glaucoma.
• Patients who are significantly below their ideal body weight (BMI < 17)..
• Serious psychiatric or medical conditions that could interfere with treatment.

2 years