This phase II trial tests how well venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax works in treating patients with newly diagnosed monocytic acute myeloid leukemia (AML) and active signaling mutated AML. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as cladribine, cytarabine and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed monocytic AML and active signaling mutated AML.
Ability to comprehend the investigational nature of the study and provide informed consent (i.e., participant or legally authorized representative [LAR]). Written informed consent must be obtained prior to any study-specific procedures or interventions
Eligible AML patients of all races and ethnic groups will be considered for participation, irrespective of gender identity
Newly diagnosed, histologically confirmed monocytic AML, as defined by World Health Organization (WHO), or active signaling mutated AML defined as AML with mutation(s) to N/KRAS, FLT3 ITD/TKD, NF1, PTPN11 or CBL
Ineligible for standard of care induction therapy using intensive chemotherapy (IC) or unwilling to undergo IC induction therapy. Ineligible for IC is defined as
Symptomatic central nervous system involvement with AML
Prior treatment for AML, with the exception of cytoreduction for proliferative disease (per institutional protocol) with any of the following: Hydroxyurea, hematopoietic growth factors, leukapheresis
Another active malignancy within the previous 5 years of C1D1
Investigational therapy within 28 days of C1D1, or within 5 half-lives or longer, if known
OHSU Knight Cancer Institute
Lead sponsor
Oregon Health and Science University
Collaborator
AbbVie
Collaborator