GLAD-AML - Glasdegib (Pf-04449913) With Two Standard Decitabine Regimens for Older Patients With Poor-risk Acute Myeloid Leukemia

Inclusion Criteria: * Patients must have a morphologically-confirmed diagnosis of AML according to WHO 2016 classification with poor-risk disease as defined by the cytogenetic or molecular abnormalities (excluding FLT3-mutated AML). * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2. * Adequate Renal Function: a. Calculated creatinine clearance (determined by MDRD) ≥50mL/min/1.73m2, or serum creatinine \<1.5x upper limit of normal (ULN); * Adequate Liver Function: 1. Total serum bilirubin ≤ 2.0 x ULN (unless the bilirubin is principally unconjugated and there is strong suspicion of sub-clinical hemolysis or the patient has documented Gilbert's disease); 2. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3.0 x ULN; 3. Alkaline phosphatase ≤ 3.0 x ULN. * Serum or urine pregnancy test (for female patients of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) negative at screening. * Males and female patients both of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 180 days after the last dose of decitabine and the last dose of glasdegib, whichever occurs later. * Female patients who are not of childbearing potential (i.e. meet at least 1 of the following criteria): 1. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 2. Have medically confirmed ovarian failure; 3. Have achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women. Exclusion Criteria: * Patients who are candidates for and willing to receive intensive induction chemotherapy. * Prior use of a hypomethylating agent. * Prior use of cytotoxic chemotherapy for any myeloid malignancy (prior immunosuppressive therapy is permitted provided that treatment is stopped within 8 weeks from study entry; hydroxyurea is allowed through the end of cycle 1 on study). * Previous hematopoietic stem cell transplant. * Prior treatment with a licensed or experimental smoothened inhibitor (SMOi) and/or hypomethylating agent (HMA). * Participation in a clinical study involving an investigational drug(s) (Phases 1-4) within 4 weeks prior to study entry or within 5 half-lives of the investigational agent, whichever is greater. * Major surgery or radiation within 12 weeks prior to study entry. * Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support. * Treatment with hematopoietic growth factors including: erythropoietin, granulocyte colony stimulating factor (G-CSF), and granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 3 weeks prior to study entry. * Any ongoing medical condition requiring chronic use of moderate to high dose steroids (defined as ≥10 mg/day of prednisone or equipotent dose of another corticosteroid). * Any anti-cancer treatment within 2 weeks prior to study entry (including hydroxyurea as above). * Current use or anticipated requirement for drugs that are known moderate to strong CYP3A4 inducers (Appendix 2). * Presence of concurrent active malignancy requiring active systemic therapy * Patients with known active, uncontrolled bacterial, fungal or viral infection, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. * Known uncontrolled central nervous system (CNS) involvement. * Poorly-controlled active medical conditions that as per investigator judgement would interfere with the conduct of the study. * Active cardiac dysrhythmias of NCI CTCAE Grade ≥2 (e.g. atrial fibrillation) or QTcF interval \>470 msec. * Pregnant or breastfeeding female patients.