Phase I Trial of Pacritinib in Combination With Venetoclax and Azacitidine for the Treatment of Accelerated and Blast Phase Myeloproliferative Neoplasms

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Subjects must have accelerated phase MPN as defined by 10-19% blasts or blast phase MPN (AML) as defined by ≥ 20% blasts in the blood or bone marrow by manual aspirate differential, immunohistochemistry staining, or flow cytometry, with a documented prior diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or primary myelofibrosis (PMF), The absence of a spleen, lack of splenomegaly, or history of splenic irradiation is not exclusionary. * Subjects with blast phase MPN must be newly diagnosed/untreated (no prior blast reduction therapy for blast phase disease except for hydroxyurea and/or a JAK inhibitor; treatment of a prior accelerated phase is allowed). Prior treatment with a hypomethylating agent (with or without a JAK inhibitor) is allowed for accelerated phase MPN. Prior treatment with any JAK inhibitor (including pacritinib) is allowed for any phase of disease (chronic, accelerated, or blast); however, must not have discontinued pacritinib due to toxicity. If a participant previously required dose reduction during pacritinib therapy and tolerated it well, then may enroll into a cohort utilizing that dose level or lower. * WBC \< 25 x 109/L prior to treatment initiation- subjects with WBC ≥ 25 x 109/L may still be eligible after receiving cytoreduction measures such as hydroxyurea and/or leukapheresis if WBC becomes \< 25 x 109/L prior to treatment initiation. C…