selective inhibitor of nuclear export (sine) selinexor (kpt-330) in patients with myelodysplastic syndromes

Conditions: Myelodysplastic Syndromes

Summary: 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.


Eligibility criteria:
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.

Keywords: selinexor (kpt-330) selective inhibitor of nuclear export (sine) 14-005