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