Study of the Safety of PIM447 in Combination With Ruxolitinib (INC424) and LEE011 in Patients With Myelofibrosis

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * Patient must be diagnosed with JAK2V617F-positive primary or secondary MF. * Dose-escalation and Expansion parts: Patients with a \< 35% reduction in spleen volume by MRI/CT or \< 50% reduction in spleen size by physical exam, with or without corresponding symptomatic improvement, after at least 6 months of treatment with single agent ruxolitinib at an optimal dose level in line with the label recommendations. Expansion parts only: Ruxolitinib-naive patients and patients who have been previously treated with single agent ruxolitinib and are relapsed and/or refractory. * Patients must have splenomegaly measuring at least 5 cm by MRI at baseline. * Have adequate bone marrow function: * Platelets ≥ 100,000 mm3 without the assistance of growth factors or platelet transfusions * Absolute Neutrophil Count (ANC) ≥ 1500/mm3 without growth factor support within 7 days prior to testing * Hemoglobin ≥ 9 g/dL. Exclusion Criteria: * Systemic antineoplastic therapy (including unconjugated therapeutic antibodies, toxin immunoconjugates, and alpha-interferon) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment * Major surgery within 2 weeks before the first dose of either study drug. * Patients who have had splenic irradiation within 2 weeks prior to Screening or prior splenectomy. * Patients with AML, MDS, or peripheral blasts ≥ 10 % * Prior autologous or allogeneic stem cell transplant at any time. * Patients who are currently receiving treatment with a prohibited medication that cannot be discontinued at least one week prior to the start of treatment: * substrates of CYP3A4/5, CYP2B6 or CYP2D6 that have a narrow therapeutic window * strong inhibitors of CYP3A4/5 or CYP2D6 * potent inducers of CYP3A4/5 or CYP2D6 * Serum total bilirubin \> 1.5 x upper limit of normal (ULN) except in patients with Gilbert's syndrome who are excluded if the total bilirubin is \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN, or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or ALT (SGPT) \> 3 x ULN, except in patients with MF involvement of the liver who are excluded if AST or ALT \> 5 x ULN. * Serum creatinine \> 1.5 x ULN or calculated creatinine clearance \< 60 ml/min according to Cockcroft-Gault equation * Electrolyte abnormalities CTCAE grade ≥ 2 (e.g. serum potassium, magnesium and calcium) unless they can be repleted during screening and are deemed not clinically significant by the Investigator.