A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML

Inclusion Criteria:

* Potential participants must have newly diagnosed, previously untreated acute myeloid leukemia (AML) (excluding M3); Must have adverse-risk AML defined as poor-risk karyotype (complex, monosomal or other known poor risk cytogenetic abnormality), poor-risk mutations/fusion genes or known history of antecedent hematologic disorder, or treatment related AML, or be ≥60 years of age; Cytogenetics, FISH or mutational analysis confirming adverse risk features must have been done within 90 days prior to enrollment.
* May not have undergone any prior therapy for their AML other than hydroxyurea. However, if patients had an antecedent myelodysplastic syndrome (MDS), prior treatment with a hypomethylating agent or any other therapy (with the exception of allogeneic stem cell transplant) used to treat their MDS is allowed.
* Age ≥18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Life expectancy of greater than 2 months
* Must have normal organ function
* Able and willing to adhere to the study visit schedule and other protocol requirements
* Baseline left ventricular ejection fraction (LVEF) ≥ 50%
* Women of child-bearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU)mL) within 10 days and again within 24 hours prior to beginning study treatment. Participants of childbearing potential must practice recommended contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Breastfeeding mothers must agree to discontinue nursing if the mother is treated with selinexor.
* Ability to understand and the willingness to sign a written informed consent document
* Able to swallow capsules and have no evidence of GI tract abnormality that would alter the absorption of oral medications
* Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 x upper limit of normal (ULN)

Exclusion Criteria:

* May not be receiving any other investigational agents
* Documented central nervous system (CNS) involvement of AML
* AML with favorable risk cytogenetic abnormalities including t(15;17), t(8;21) or inv(16)
* Potential participants who are in the blast phase of chronic myeloid leukemia
* Major surgery within 2 weeks of first dose of study drug; must have recovered from the effects of any surgery performed greater than 2 weeks prior
* White blood cell (WBC) count ≥50,000 on hydroxyurea
* Predicted inability to tolerate standard induction chemotherapy with daunorubicin and cytarabine
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* HIV-positive, receiving combination anti-retroviral therapy
* No other malignancies in addition to AML that are currently requiring treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
* History of allogeneic stem cell transplant for MDS or any other antecedent hematologic disorder.