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

PRIMARY OBJECTIVE: I. To estimate the proportion of patients with previously-untreated chronic phase chronic myeloid leukemia (CML) who achieve molecular response 4 (MR4) after 6-months of the combination of decitabine and cedazuridine (ASTX727) and dasatinib 50 mg daily. SECONDARY OBJECTIVES: I. To estimate the proportion of patients with previously-untreated chronic phase CML who achieve MR4 after both the 3-months of the combination of ASTX727 and dasatinib 50 mg daily. II. To estimate cumulative overall rate of molecular response 4.5 (MR4.5). III. To estimate the 12-months major molecular response (MMR) rate. IV. To estimate the proportion of patients with MR4.5 at 6-, 12-, 18-, 24-, and 36-months of therapy. V. To estimate the proportion of patients with sustained MR4.5 of 3 years and more. VI. To estimate the treatment-free remission rate (TFR), time to progression, and overall survival. VII. To assess the safety of this combination. OUTLINE: Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Beginning cycle 4, patients also receive decitabine and cedazuridine PO QD on days 1-3. Cycles repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days for up to 12 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.