Inclusion Criteria:

   - Participants must have a diagnosis of AML, MDS, ALL or MPAL and must have disease that
   has relapsed or is refractory to chemotherapy, or that has relapsed after
   hematopoietic stem cell transplantation (HSCT)

      - Refractory disease is defined as persistent disease after at least two courses of
      induction chemotherapy.

      - Patients with AML, MPAL or MDS are eligible at first or subsequent relapse,
      whereas patients with ALL are eligible at second or subsequent relapse or any
      relapse that is refractory to salvage chemotherapy.

      - Patients with AML or ALL must have ≥ 5% leukemic blasts in the bone marrow or
      increasing levels of MRD in the bone marrow as assessed by flow cytometry. If an
      adequate bone marrow sample cannot be obtained, patients may be enrolled if there
      is unequivocal evidence of leukemia in the peripheral blood.

   - Adequate organ function defined as the following:

      - Direct bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)

      - AST (SGOT)/ALT (SGPT) < 3 x IULN

      - Creatinine within normal institutional limits for age

   - Prothrombin time (PT) and partial thromboplastin (PTT) ≤ 1.5 x IULN.

   - Age criteria: Patients treated at collaborating sites and current St. Jude patients
   who are on therapy or within 3 years of completion of therapy must be ≤ 24 years old.
   All other St. Jude patients must be < 21 years old.

   - Patients must be able to swallow tablets.

   - Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥
   50% for patients who are > 16 years old.

   - Patients must have fully recovered from the acute effects of all prior therapy.

   - For patients who have received prior HSCT, there can be no evidence of GVHD and
   greater than 60 days must have elapsed since the HSCT.

Exclusion Criteria:

   - History of cerebellar toxicity or cerebellar neurological findings on exam.

   - Must not be pregnant or breastfeeding. 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 with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic
   leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow
   failure syndromes are not eligible.

   - Use of investigational agents, with the exception of gemtuzumab ozogamicin, within 30
   days.

   - Any significant concurrent disease, illness, or psychiatric disorder that would
   compromise patient safety or compliance, study participation, follow up, or
   interpretation of study research.

   - Unstable cardiovascular function:

      - symptomatic ischemia

      - congestive heart failure NYHA Class > 3

      - 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 are acceptable.

   - Known human immunodeficiency virus (HIV) infection (pre-study testing not required).

   - Patients with malabsorption syndrome, or any other disease significantly affecting
   gastrointestinal function.

   - Prior treatment with selinexor.