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

A Phase I Study of Venetoclax Combined With Vyxeos (CPX-351) for Children, Adolescents and Young Adults With Relapsed or Refractory Acute Leukemia

This study evaluates the safety and tolerability of combining venetoclax with Vyxeos (CPX-351) in pediatric and young adult patients with acute leukemia that has come back or not responded to treatment.

This is a single-institution Phase I pilot study designed to test the safety and tolerability of combining venetoclax with Vyxeos (CPX-351, cytarabine and daunorubicin liposome) for the treatment of relapsed/refractory acute leukemia in young patients. Subjects will receive a single course of study therapy consisting of daily, oral or crushed venetoclax at an assigned dose level with a 3-day ramp-up to target dose and Vyxeos administered intravenously at the established dose on Days 1, 3, and 5. In addition to safety and tolerability, the overall response rate to these therapies will be estimated. Pharmacokinetic (PK) analysis will also be conducted to define the drug clearance of venetoclax in this combination.

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