Overview
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.
Description
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.
Eligibility
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
- 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