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

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 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 1-39 years

- Diagnosis of one of the following:

- Acute myeloid leukemia (AML)

- Acute undifferentiated leukemia (AUL)

- Mixed phenotype acute leukemia (MPAL)

- T-cell acute lymphoblastic leukemia (T ALL)

- Early thymocyte precursor (ETP) ALL

- KMT2A-rearranged ALL

- Disease status

- Relapsed/Refractory AML, MPAL and AUL

- Untreated therapy related AML

- Relapsed/Refractory KMT2A-rearranged ALL, T-cell ALL, ETP 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:

- Acute Promyelocytic Leukemia (APML)

- Acute leukemia with CNS status 3 involvement

- Philadelphia chromosome positive leukemia (Ph+ ALL, 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

- Unable to swallow tablets

- 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