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 patie…