ASTX727 and Dasatinib for the Treatment of Newly Diagnosed Philadelphia Chromosome or BCR-ABL Positive Chronic Myeloid Leukemia in Chronic Phase

This phase II trial studies the effect of ASTX727 and dasatinib in treating patients with newly diagnosed Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in chronic phase. Philadelphia chromosome positive and BCR-ABL positive are types of genetic mutations (changes). Chemotherapy drugs, such as ASTX727, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 and dasatinib may help to control Philadelphia chromosome-positive chronic myeloid leukemia or BCR-ABL positive chronic myeloid leukemia in chronic phase.

Inclusion Criteria: * Diagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis ≤12 months). Except for hydroxyurea and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior therapy, defined as \< 1 month (30 days) of prior Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI) * Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution at diagnosis (early disease) and no other criteria for accelerated phase will be eligible for this study. * Eastern Cooperative Oncology Group (ECOG) performance of 0-2 * Adequate end organ function, defined as the following: total bilirubin \ 12 months), accelerated (except as noted in inclusion criteria 4.1) or blast phase are excluded. The definitions of CML phases are as follows: * Early chronic phase: time from diagnosis to therapy ≤ 12 months * Late chronic phase: time from diagnosis to therapy \> 12 months * Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow * Accelerated phase CML: presence of any of the following features: * Peripheral or marrow blasts 15% or more * Peripheral or marrow basophils 20% or more * Thrombocytopenia \< 100 x 10\^9/L unrelated to therapy * Documented extramedullary blastic disease outside liver or spleen