Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)

1. Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS).
2. Palpable splenomegaly of more than or equal to 5 cm below left costal margin on physical exam
3. Understanding and voluntary signing an Institutional Review Board (IRB)-approved informed consent form.
4. Age equal to or more than 18 years at the time of signing the informed consent.
5. Disease-free of other malignancies.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. Negative pregnancy test in females of childbearing potential (FCBP). Male patients with female partners of child-bearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Acceptable forms of contraception include 1 highly effective method such as an intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or partner's vasectomy and at least 1 additional approved barrier method such as a latex condom, diaphragm, or cervical cap. Female patients of childbearing potential must not be breast-feeding or planning to breast feed and must have a negative pregnancy test ≤7 days before first study treatment.
8. QTcF interval equal to or less than 470 msec
9. Normal serum potassium magnesium levels
10. Adequate organ function as demonstrated by the following: Direct bilirubin equal to or less than 2.0 mg/dL, Serum creatinine equal to or less than 2.0 mg/dL., Alanine transaminase (SGPT) equal to or less than 3 x upper limit of normal (unless considered to be related to MF or patient has known history of Gilberts)
11. Platelets >/= 50000/uL
12. Absolute Neutrophil count (ANC) >/= 1000/uL

Exclusion Criteria:

1. Prior therapy with a JAK inhibitor (other than ruxolitinib for less than 3 months duration and currently on it) or HDACi. Patients that are currently on ruxolitinib for less than 3 months of therapy are eligible.
2. Use of any other standard or experimental therapy within 14 days of starting study therapy.
3. Lack of recovery from all toxicity from previous therapy to grade 1 or baseline.
4. Suspected pregnancy, pregnant or lactating females.
5. Any condition, including the presence of laboratory abnormalities, which in the opinion of the treating physician places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
6. Known positive for HIV or infectious hepatitis, type A, B or C.
7. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
8. Cardiopulmonary function criteria: • Current unstable arrhythmia requiring treatment • History of symptomatic congestive heart failure • History of myocardial infarction within 6 months of enrollment • Current unstable angina • Family history of long QT syndrome