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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF), post-essentialthrombocythemia-myelofibrosis (PET-MF), chronic myelomonocytic leukemia, polycythemiavera, or essential thrombocytosis according to the 2008 World Health Organizationcriteria
• Subject has at least 2 symptoms with a score ≥ 3 or a total score of ≥ 12, as measuredby the MFSAF(Myelofibrosis Symptom Assessment Form) v4.0
• Subject classified as intermediate-2 or high-risk MF, as defined by the DynamicInternational 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 atleast 12 weeks with documented disease progression OR subject must have appearance ofnew 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 lineJAK2 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 HIPAAconsent document

Exclusion Criteria:

• Patients may not be receiving any other investigational agents
• Subjects must not be experiencing toxicity due to prior therapy that has not resolvedto ≤Grade 1 by study registration, with the exception of sensory neuropathy related toprevious systemic therapy exposure, alopecia and fatigue.
• Patients that have transformed to Acute Myeloid Leukemia defined by >20% blasts counton 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, unstableangina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/socialsituations that would limit compliance with study requirements.
• Patients with history of hemorrhagic stroke and evidence of uncontrolled bleeding aswell as bleeding disorder
• Known HIV positive patients on combination antiretroviral therapy are ineligiblebecause these patients are at increased risk of lethal infections when treated withmarrow-suppressive therapy.
• Pregnant or breast-feeding.