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.