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

Exclusion Criteria

• •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.
• •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.