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

Prior treatment

• 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.
• 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.

Other illness

• Patients with history of hemorrhagic stroke and evidence of uncontrolled bleeding as well as bleeding disorder

Lab values

• Patients that have transformed to Acute Myeloid Leukemia defined by \>20% blasts count on peripheral blood smear or bone marrow biopsy evaluation

Age

• 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.

Other

• Pregnant or breast-feeding.

• 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