A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia

Exclusion Criteria

• •Subjects with any of the following characteristics/conditions will not be included in the study:
• •1. Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016 classification).
• •2. AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.
• •* Complex genetics may include t(9;22) cytogenetic translocation.
• •3. Subjects with known active CNS leukemia.
• •4. Participation in other clinical studies involving other investigational drug(s) (Phases 1 4) within 4 weeks prior study entry and/or during study participation.
• •5. Subjects known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.
• •6. Subjects with another active malignancy on treatment with the exception of basal cell carcinoma, non melanoma skin cancer, cervical carcinoma in situ. Other prior or concurrent malignancies will be considered on a case by case basis.
• •7. Any one of the following ongoing or in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, symptomatic arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as \<50 bpms.
• •8. Subjects with an active, life threatening or clinically significant uncontrolled systemic infection not related to AML.
• •9. Subjects with left ventricular ejection fraction (LVEF) \<50% are excluded from the Intensive Chemotherapy Study only.
• •10. Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the Intensive Chemotherapy Study only.
• •11. Known malabsorption syndrome or other condition that may significantly impair absorption of study medication in the investigator's judgment (eg, gastrectomy, lap band, Crohn's disease) and inability or unwillingness to swallow tablets or capsules.
• •12. Current use or anticipated requirement for drugs that are known strong CYP3A4/5 inducers.
• •13. Concurrent administration of herbal preparations.
• •14. Major surgery or radiation within 4 weeks of starting study treatment.
• •15. Documented or suspected hypersensitivity to any one of the following:
• •* For subjects assigned to intensive chemotherapy, documented or suspected hypersensitivity to cytarabine (not including drug fever or exanthema, including known cerebellar side effects) or daunorubicin.
• •* For subjects assigned to non intensive chemotherapy, documented or suspected hypersensitivity to azacitidine or mannitol.
• •16. Known active drug or alcohol abuse.
• •17. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• •18. Pregnant females or breastfeeding female subjects.
• •19. Known recent or active suicidal ideation or behavior.
• •20. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.