Selinexor With Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

Inclusion criteria

• Signed, written informed consent in accordance with federal, local, and institutional guidelines
• Patients with newly diagnosed or relapsed/refractory AML, except acute promyelocytic leukemia (APL), requiring intensive induction chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• Creatinine clearance > 30 cc/min calculated using the Cockcroft and Gault (1976) formula or measured
• Total bilirubin =< 2 mg/dl unless high indirect bilirubin is due to a congenital disorder
• Transaminases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) =< 3.0 x upper limit of normal (ULN) unless due to leukemia infiltration
• Prothrombin time (PT) and partial thromboplastin time (PTT) =< 2 x ULN
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
• It is important patients understand the need to use birth control while on this study; female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening (< 3 days prior to first dose), male patients with partners of childbearing potential must agree to use effective contraception during the study period and a period of 3 months after the last dose of study drug; 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

• Treatment with any investigational agent within two weeks prior to first dose in this study; hydroxyurea is allowed to control the AML prior to treatment on the study
• AML central nervous system (CNS) involvement
• Major surgery within 2 weeks of first dose of study drug; patients must have recovered from the effects of any surgery performed greater than 2 weeks previously
• Patient has a concurrent advantage active malignancy under treatment
• Unstable cardiovascular function:

• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block/right bundle branch block [left anterior fascicular block (LAFB)/right bundle branch block (RBBB)] will not be excluded), or
• Congestive heart failure (CHF) New York Heart Association (NYHA) class >= 3, or
• Myocardial infarction (MI) within 3 months
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
• Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen)
• Known human immunodeficiency virus (HIV) infection
• Any medical condition which, in the investigator's opinion, could compromise the patient's safety
• Patients unable to swallow tablets or patients with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function
• Seizure or cerebrovascular accident (CVA) in the last year