Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)

Inclusion Criteria:

* Confirmed diagnosis of:

  * Primary MF or post-PV/ET MF classified as high risk, intermediate-2 risk, or intermediate-1 risk who are unresponsive or unable to receive current therapy which may or may not include ruxolitinib OR
  * MPN/MDS Syndrome (chronic myelomonocytic leukemia \[CMML\], juvenile myelomonocytic leukemia \[JMML\], atypical chronic myeloid leukemia \[aCML\], or MDS/MPN unclassifiable)
* ECOG 0-3
* Required laboratory values:

  * Neutrophil count of ≥ 0.5 x 109/L
  * Bone marrow blood blast count \< 20%
  * AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
  * Total creatinine \< 2.5mg/dL
  * Total bilirubin ≤ 2.0 x ULN
* Age ≥ 18 years old at enrollment.
* If female, must be:

  * postmenopausal for at least 1 year before the screening visit OR
  * surgically sterile OR
  * agreeable to practicing 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment.
* Able to swallow pills.
* If a sexually active heterosexual male, must be agreeable to practicing 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* Prior treatment with more than two JAK2 inhibitors or with pacritinib
* Known positive status for human immunodeficiency virus (HIV)
* Chronic, active, or acute viral hepatitis A, B, or C infection, or a hepatitis B or C carrier
* Use of chemotherapy, biologic therapy, radiation therapy, erythropoietin or related erythropoiesis stimulating agents, or investigational therapy within 2 weeks of the first dose of study drug
* History of allogeneic stem cell transplant or transplant eligible
* Currently receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib or other agents used in the study
* Ongoing gastrointestinal medical condition such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation that could interfere with absorption of oral medication
* Active bleeding that requires hospitalization during the screening period
* Cardiovascular disease, including recent history of or currently clinically symptomatic and uncontrolled congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction. Patients with CTCAE grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety. Patients will e excluded if they have ongoing cardiac dysrhythmias of CTCAE grade ≥ 3, corrected QT interval (QTc) prolongation \> 450 ms, or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia \[defined as serum potassium \< 3.0 mEq/L that is persistent and refractory to correction\], or family history of long QT interval syndrome).
* Other malignancy requiring active treatment at time of study entry
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or serious medical or psychiatric illness/social situations that would limit compliance with study requirements.
* Life expectancy \< 6 months
* Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
* Receiving treatment with any potent CYP3A4 inhibitors within 7 days of the first dose of study drug
* Patients with MF who are eligible for enrollment in the pacritinib "PERSIST-2" study at WUSM (NCT02055781) HRPO 201406075.