Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes

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.