SHS_492416 MAWR CPFI 18010
A Randomized (1:1), Double-blind, Multi-center, Placebo Controlled Study Evaluating Intensive Chemotherapy With Or Without Glasdegib (Pf-04449913) Or Azacitidine (Aza) With Or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia
A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia.
• Subjects with untreated AML according to the World Health Organization (WHO) 2016 Classification2, including those with:
• AML arising from MDS or another antecedent hematologic disease (AHD).
• AML after previous cytotoxic therapy or radiation (secondary AML).
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) 3 x upper limit of normal (ULN), excluding subjects with liver function abnormalities due to underlying malignancy.
• Total serum bilirubin 2 x ULN (except subjects with documented Gilbert's syndrome).
• Estimated creatinine clearance 30 mL/min as calculated using the standard method for the institution.
• QTc interval 470 msec using the Fridericia correction (QTcF).
• All anti cancer treatments (unless specified) should be discontinued 2 weeks from study entry.
• Male and female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 180 days after the last dose.
• Acute Promyelocytic Leukemia (APL) and APLwith PML RARA, subjects (WHO 2016 classification).
• AML with BCR ABL1 or t(9;22)(q34;q11.2) as a sole abnormality.
• Complex genetics may include t(9;22) cytogenetic translocation.
• Subjects with known active CNS leukemia.
• Subjects known to be refractory to platelet or packed red cell transfusions per Institutional Guidelines, or a patient who refuses blood product support.
• 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.
• 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.
• Subjects with an active, life threatening or clinically significant uncontrolled systemic infection not related to AML.
• Subjects with left ventricular ejection fraction (LVEF) <50% are excluded from the Intensive Chemotherapy Study only.
• Cumulative anthracycline dose equivalent of 550 mg/m2 of daunorubicin for the Intensive Chemotherapy Study only.
• 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.
• Major surgery or radiation within 4 weeks of starting study treatment.
• Pregnant females or breastfeeding female subjects.
Raya Mawad, M.D.