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

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.