A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) versus Treatment Choice in Adults with Previously Treated Acute Myeloid Leukemia

INTERVENTION: Intervention name : SGI‐110 INN of the intervention : Guadecitabine Dosage And administration of the intervention : 60 mg/m2 SC daily on Days 1‐5 and Days 8‐12 (first cycle) Control intervention name : Intermediate or high dose Cylocide INN of the control intervention : Cytarabine Dosage And administration of the control intervention : 1‐1.5 g/m2 every 12 hours or up to 6 g/m2/day for 6 days or less, maximum 36 g/m2 per cycle Control intervention name : Novantron, Sandoz, and Cylocide INN of the control intervention : Mitoxantrone, etoposide, and cytarabine Dosage And administration of the control intervention : mitoxantrone 6‐12 mg/m2 IV (recommended 8 mg/m2), etoposide 80‐200 mg/m2 IV (recommended 100 mg/m2), and cytarabine 1000 mg/m2 IV; each daily for 5 days (Days 1‐5) Control intervention name : Low dose Cylocide INN of the control intervention : Cytarabine Dosage And administration of the control intervention : 20 mg SC or IV twice daily on Days 1‐10 CONDITION: acute myeloid leukemia PRIMARY OUTCOME: OS, defined as the number of days from date of randomization to date of death SECONDARY OUTCOME: ‐ EFS defined as the number of days from randomization to the earliest of disease progression, treatment discontinuation, start of alternative anti‐leukemia therapy (except HCT), or death.; ‐ Survival rate at 1 year after randomization. (Subjects will also be followed long term to estimate 2‐year survival rate.); ‐ NDAOH.; ‐ Transfusion independence rate, calculated based on the number of subjects without red blood cell (RBC) or platelet transfusion for any period of 8 weeks after treatment.; ‐ CR rate based on modified International Working Group (IWG) 2003 AML Response Criteria.; ‐ CRc (CR+CRi+CRp) rate.; ‐ HCT rate. (In subjects who undergo HCT, time to stem cell engraftment and 100‐day mortality rate post HCT will also be assessed.); ‐ Duration of CR, defined as the time from first CR to time of relapse.; ‐ Health‐related QOL by EQ‐5D (consisting of the EQ‐5D‐5L descriptive system and the EQ Visual Analogue; Scale [EQ VAS]).; ‐ Incidence and severity of adverse events (AEs).; ‐ 30‐ and 60‐day all‐cause early mortality. INCLUSION CRITERIA: ‐ History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts 20% or more). ‐ Performance status (Eastern Cooperative Oncology Group; ECOG) of 0‐2. ‐ Subjects with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction. ‐ Subjects must have either PB or BM blasts 5% or more at time of randomization. ‐ Creatinine clearance or glomerular filtration rate 30 mL/min or more as estimated by the Cockroft‐Gault (C‐G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD‐EPI (the Chronic Kidney Disease Epidemiology Collaboration). ‐ Women of child‐be