The treatment of mixed phenotype acute leukemia (MPAL) is challenging due to the presence of disease characteristics of both myeloid and lymphoid leukemia. Regimens historically used to treat acute lymphoblastic leukemia are often used to treat MPAL, particularly for patients whose diseases also possess the Philadelphia chromosome (Ph+). Here we present a novel regimen, HAM-pegA plus dasatinib, for the treatment of two patients with newly diagnosed Ph+ MPAL. This regimen is a blend of both myeloid-targeted and lymphoid-targeted chemotherapy agents, and is given as a single cycle of intensive chemotherapy followed by oral dasatinib maintenance therapy. Without proceeding to allogeneic transplant, this regimen produced durable remissions of 18 months and longer. This novel regimen offers an exciting alternative to other intensive regimens that require multiple cycles of intensive chemotherapy and allogeneic transplant in first remission.