Venetoclax Combined With Vyxeos (CPX-351) for Participants With Relapsed or Refractory Acute Leukemia

Inclusion Criteria:

* Ages 1 Year to 39 Years
* Diagnosis of one of the following:

  * Acute myeloid leukemia (AML), any subtype except

    * Patients with acute promyelocytic leukemia (APML) are NOT eligible
    * Patients with ML-DS are NOT eligible
  * Myeloid sarcoma
  * Acute leukemia of ambiguous lineage (ALAL)

    * Acute undifferentiated leukemia (AUL)
    * T/myeloid mixed phenotype acute leukemia (MPAL)
    * B/myeloid MPAL
    * MPAL with KMT2A-rearrangement MPAL with t (9;22) are NOT eligible
  * T-cell acute lymphoblastic leukemia (T ALL)
  * Early thymocyte precursor (ETP) ALL
  * KMT2A-rearranged ALL
* Disease Status

  * Relapsed/Refractory AML, MPA, and AUL
  * Untreated therapy related AML
  * Relapsed/Refractory KMT2A-rearranged ALL, T-cell ALL, ETEP ALL
* Karnofsky/Lanksy performance level score of greater than or equal to 50 percent.
* Prior therapy requirements

  * Fully recovered from acute toxicities of Hematopoietic Stem Cell Transplant (HSCT) or Anthracycline Exposure
  * 14 days must have elapsed since the completion of systemic cytotoxic therapy other than hydroxyurea, decitabine or azacitidine
  * 2 weeks must have elapsed for local palliative radiotherapy (RT); 6 months must have elapsed if prior craniospinal RT or if 50% radiation of pelvis, and at least 6 weeks must have elapsed if other substantial bone marrow radiation
* Adequate renal, liver, cardiac, and central nervous system (CNS) function

Exclusion Criteria:

* Diagnosis of one of the following:

  * Myeloid Leukemia associated with Down Syndrome (ML-DS)
  * Acute Promyelocytic Leukemia (APML)
  * Acute leukemia with CNS status 3 involvement
  * Philadelphia chromosome t(9;22) positive leukemia (Ph+ ALL, AML, MPAL, or AUL)
  * Fanconi Anemia, Shwachman-Diamond syndrome, or any other bone marrow failure syndrome or DNA repair disorder
  * Wilson's Disease or other copper-metabolism disorder
* Pregnant or breastfeeding
* Uncontrolled infection
* Received greater than 13.6 Gray (Gy) prior radiation to the mediastinum
* Receipt of growth factors within 7 days prior to enrollment
* Currently receiving another investigational drug
* Currently receiving anti-cancer agents (with the exception of intrathecal (IT) agents or hydroxyurea)
* Unable to comply with the safety monitoring requirements of the study