Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition

Eligibility Criteria

• * Patients must have histologically or cytologically confirmed primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF), post-essential thrombocythemia-myelofibrosis (PET-MF), chronic myelomonocytic leukemia, polycythemia vera, or essential thrombocytosis according to the 2008 World Health Organization criteria
• * Subject has at least 2 symptoms with a score ≥ 3 or a total score of ≥ 12, as measured by the MFSAF(Myelofibrosis Symptom Assessment Form) v4.0
• * Subject classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+70).
• * Age \> 18 years.
• * ECOG (Eastern Cooperative Oncology Group) performance status 0-2
• * Subject must have received prior treatment with a single JAK2 inhibitor 4.1.6 for at least 12 weeks with documented disease progression OR subject must have appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in subjects with no evidence of splenomegaly prior to the initiation of any first line JAK2 inhibitor
• * Baseline QTc (corrected QT interval) \<0.47 seconds (Bazett formula)
• * Patients must have normal organ function as defined in protocol.
• * Ability to understand and willingness to sign a written informed consent and HIPAA consent document
• * Patients may not be receiving any other investigational agents
• * Subjects must not be experiencing toxicity due to prior therapy that has not resolved to ≤Grade 1 by study registration, with the exception of sensory neuropathy related to previous systemic therapy exposure, alopecia and fatigue.
• * Patients that have transformed to Acute Myeloid Leukemia defined by \>20% blasts count on peripheral blood smear or bone marrow biopsy evaluation
• * Uncontrolled inter-current illness including, but not limited to, any other malignancy (with the exception of hormonal therapy for breast cancer/prostate cancer in remission \>1 year and for non-hormonal therapies for other cancers in remission for \>3 years), other ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• * Patients with history of hemorrhagic stroke and evidence of uncontrolled bleeding as well as bleeding disorder
• * Known HIV positive patients on combination antiretroviral therapy are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• * Pregnant or breast-feeding.