Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial)

Inclusion Criteria: * Male or female patients aged ≥ 18 years old * Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed * Intermediate-2 and higher by IWG-MRT Post PV/ET MF and PMF patients either in 1. Chronic Phase (MF-CP) 2. Accelerated Phase (MF-AP) * Patients must meet the following laboratory criteria: 1. ANC ≥ .750 x 109/L 2. Platelets ≥ 75 x 109/L 3. Creatinine ≤ 1.5 x ULN, 4. AST and ALT ≤ 2.5 x ULN 5. Serum bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome and evidence of hemolysis) 6. Serum potassium ≥ LLN 7. Total serum calcium \[corrected for serum albumin\] or ionized calcium ≥LLN, 8. Serum magnesium ≥ LLN 9. Serum phosphorus ≥ LLN 10. Free T4 within normal limits * ECOG Performance Status of ≤ 3 * Any prior therapy with JAK2-TKI, hypomethylating agents, HDACI, mTORi, or iMiDs is allowed as long as it is greater than 3 weeks since last dose of administration and in the case of a JAK2-TKI or HDACI that discontinuation was not due to non-hematologic drug toxicity. An exception to this criteria are patients currently on at least 10mg BID of ruxolitinib for greater than 3 months and who have not shown an optimal response (i.e. without 50% reduction in palpable splenomegaly or 50% reduction in symptom burden). With a reduction of ruxolitinib to 10mg BID these patients may enter onto the study without stopping ruxolitinib Exclusion Criteria: * Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANOBINOSTAT treatment. * Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: 1. With permanent cardiac pacemaker 2. Resting bradycardia defined as \<50 beats per minute 3. QTcF \>450 msec on screening ECG 4. Complete Left bundle branch block, bifascicular block 5. Any clinically significant ST segment and/or T-wave abnormalities 6. Presence of unstable atrial fibrillation (ventricular response rate \>100 bpm). Patients with stable atrial fibrillation can be enrolled provided they do not meet other cardiac exclusion criteria. 7. Symptomatic congestive heart failure (NYHA class III-IV) * Impairment of GI function or GI disease that may significantly alter the absorption of PANOBINOSTAT or RUXOLITINIB * Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol * Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug * Concomitant use of CYP3A4 inhibitors * Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies. * Chemotherapy within 3 weeks prior to screening are excluded (other than hydroxyurea at stable doses and will be discontinued 24 hours prior to starting study drug). * Patients with an active bleeding tendency or are receiving any treatment with therapeutic doses of sodium warfarin (Coumadin®) or coumadin derivatives. Patients will be allowed to enter study on aspirin at doses of 81mg/d. * Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy * Women who are pregnant or breast-feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24hrs of receiving the first dose of study medication. * Male patients whose sexual partners are WOCBP not using effective birth control * Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix) * Disease associated with secondary MF such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease or acute leukemia (including M7 disease or acute panmyelosis with MF)