Study of CLAG + Selinexor in Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

* Histologically confirmed AML (defined using WHO criteria) with one of the following:

  * Primary refractory disease following ≤ 2 cycles of induction chemotherapy, or
  * First relapse with no prior unsuccessful salvage chemotherapy, or
  * Relapsed or refractory to hypomethylating agent, defined as a lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator
* Age between 18 and 70 years old.
* ECOG performance status ≤ 3
* Adequate organ function as defined below:

  * AST(SGOT), ALT(SGPT), total bilirubin ≤ 2 x IULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia) or Gilbert's disease
  * Creatinine clearance \>50 ml/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg) / (72 x Creatinine mg/dL); multiply by 0.85 if female.
  * Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
* To ensure that no patient will receive a dose of selinexor \>70mg/m\^2, body surface area (BSA) calculated by Dubois method must be \>1.43 m\^2
* Patients should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while on this study. It is important patients understand the need to use birth control while on this study. It is not anticipated that female patients enrolling in this study will be able to conceive. However, in the rare event that this is possible, 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.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants).
* Previous treatment with CLAG or other chemotherapy regimen containing both cladribine and cytarabine.
* Colony stimulating factors within 2 weeks of study.
* Active graft versus host disease (GVHD) after allogeneic stem cell transplantation. At least 2 months must have elapsed since completion of an allogeneic stem cell transplantation.
* Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (with the exception of hydroxyurea).
* Concurrent active malignancy under treatment except prostate or breast cancer undergoing treatment with hormonal therapy.
* Treatment with any investigational agent within three weeks prior to first dose in this study.
* Active CNS involvement with leukemia.
* Unstable cardiovascular function:

  * symptomatic ischemia, or
  * uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
  * congestive heart failure (CHF) of NYHA class ≥3, or
  * myocardial infarction (MI) within 3 months
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to KPT-330 or other agents used in the study.
* 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.
* Any medical condition which, in the investigator's opinion, could compromise the patient's safety.
* Pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within 5 days of study entry.
* Unable to swallow tablets, or diagnosed malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.
* 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.
* Serious psychiatric or medical conditions that could interfere with treatment.