Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)
Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)
The goal of this clinical research study is to learn if pracinostat, when given in
 combination with ruxolitinib, can help to control myelofibrosis (MF). The safety of this drug
 combination will also be studied.

 This is an investigational study. Pracinostat is not FDA-approved or commercially available.
 It is currently being used for research purposes only. Ruxolitinib is FDA-approved and
 commercially available to treat MF.

 The study doctor can explain how the study drugs are designed to work.

 Up to 25 participants will be enrolled in this study. All will take part at MD Anderson.
Study Drug Administration:

 If you are found to be eligible to take part in this study, you will take ruxolitinib by
 mouth 2 times each day. You may take your dose of ruxolitinib with or without food.

 You will also take pracinostat by mouth 1 time each day for 3 alternating days (for example
 Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) every 3 weeks starting on Day 1 of
 Cycle 4. You will take your dose of pracinostat in the morning, about 30 minutes before or 2
 hours after a meal. You should swallow your dose of pracinostat whole with a cup of water
 (about 8 ounces).

 You will be given a study drug diary to write down when you take your dose of study drugs and
 if you miss or vomit any doses of study drug. You must bring the diary with you to the clinic
 on Day 1 of each cycle and at the end-of-treatment visit. You will also need to bring any
 leftover pills and any empty containers of the study drugs to the clinic when the study
 doctor tells you to do so.

 Study Visits:

 There are 28 days (4 weeks) in every study cycle. You will visit MD Anderson for regular
 study visits while participating in this study during Cycles 2-7, and then once every 3
 cycles after that (Cycles 10, 13, 16, and so on).

 Once during Cycles 2-7 and then once every 3 cycles after that (Cycles 10, 13, 16, and so
 on):

 -  You will have a physical exam.

 -  You will complete the questionnaire about your quality of life.

 At your visits during Cycles 4, 5, and 6 and then once every 3 cycles starting with cycle 10
 (cycles 10, 13, 16 and so on): You will have an EKG to check your heart function.

 At your visits during Cycles 4, 5, and 7 and then every 3 cycles after that (Cycles 10, 13,
 16, and so on) blood (about 1-2 teaspoons) will be drawn for cytokine testing.

 At your visits during Cycles 7 and 13, and then every 6 cycles after that (Cycles 19, 25, 31,
 and so on), if the doctor thinks it is needed, you will have a bone marrow biopsy to check
 the status of the disease and for cytogenetic and genetic testing.

 Every 2 weeks during the first 6 cycles and then about every 3 cycles after that, blood
 (about 2-3 tablespoons) will be drawn for routine tests. In between the mandatory visits to
 MD Anderson, you may choose to have these blood draws performed at a local lab or clinic
 closer to your home. The results will be sent to the study doctor.

 Length of Treatment:

 You may continue taking the study drugs for up to 4 years. You will no longer be able to take
 the study drugs if the disease gets worse, if intolerable side effects occur, or if you are
 unable to follow study directions.

 Your participation on the study will be over after the follow-up.

 Follow-Up:

 About 30 days after your last dose of study drugs, if you are not receiving another treatment
 for MF, you will be called by the study doctor or a member of the study staff and asked about
 any side effects you may be having. This call should last about 10 minutes.
Inclusion Criteria:

 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