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

This is an interventional treatment trial for Chronic Myelomonocytic Leukemia Read More

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.