Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)
Condition: Myeloproliferative Diseases
MeSH terms: Primary Myelofibrosis; Myeloproliferative Disorders
Intervention: Ruxolitinib; Pracinostat; Questionnaire
Intervention description: Ruxolitinib taken by mouth 2 times each day in a 28-day cycle. Patients receive Ruxolitinib alone for first 3 months, and then Pracinostat added. Starting dose of Ruxolitinib based on patients' platelet count. Dose of Ruxolitinib may be increased or decreased at discretion of treating physician prior to initiation of Pracinostat.; Starting dose of Pracinostat 60 mg by mouth 1 time each day for 3 alternating days every 3 weeks starting on Day 1 of Cycle 4.; Questionnaire regarding quality of life completed at baseline, within 3 days before Day 1 of Cycles 1 - 6, and then every 3 cycles after that.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloproliferative Diseases; Myelofibrosis; MF; Primary or post essential thrombocythemia/polycythemia vera; Ruxolitinib; Jakafi; INCB018424; INC424; Pracinostat; Questionnaire; Survey

Summary:

      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.
    

Eligibility criteria:

        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