Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Leukemia of Ambiguous Lineage

Inclusion Criteria:

   - Participants must have a diagnosis of AML or acute leukemia of ambiguous lineage
   (acute undifferentiated leukemia or mixed phenotype acute leukemia) and have
   refractory leukemia, defined as persistent leukemia after at least two courses of
   induction chemotherapy; or relapsed leukemia, defined as the re-appearance of leukemia
   after the achievement of remission.

   - Patients in all categories above must have ≥ 5% blasts in the bone marrow as assessed
   by morphology or ≥ 1 blasts in the bone marrow as assessed by flow cytometry. However,
   if an adequate bone marrow sample cannot be obtained, patients may be enrolled if
   there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood. In
   addition, patients in all categories must not be eligible to undergo curative therapy,
   such as immediate SCT, because of disease burden, time needed to identify a stem cell
   donor, or other reasons.

   * Adequate organ function defined as the following:

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

   - AST (SGOT) and ALT (SGPT) ≤ 4 x ULN

   - Normal creatinine for age or a calculated creatinine clearance ≥ 60 mL/min/1.73 m2

   - Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%

      - St. Jude patients must be between 2 years and ≤ 21 years of age, on therapy
      (active patient), or within 3 years of completion of therapy. Patients treated at
      collaborating sites must be ≤ 24 years old.

      - 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
      and cannot have evidence of graft-versus-host disease (GVHD)

Exclusion Criteria:

   - Must not be pregnant or breastfeeding. Male or female of reproductive potential must
   agree to use effective contraception for the duration of study participation.

   - Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic
   leukemia, or bone marrow failure syndromes are not eligible.

   - Uncontrolled infection. Infections controlled on concurrent anti-microbial agents are
   acceptable, and anti-microbial prophylaxis per institutional guidelines are
   acceptable.

   - Impairment of GI function or GI disease that may significantly alter the absorption of
   venetoclax.