with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Considered Candidates

Primary Objective • To assess and compare efficacy (complete response [CR] rate and overall survival [OS]) between SGI-110 and TC in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy. Secondary Objectives • To assess and compare effects of SGI-110 and TC in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy with respect to the following variables: - Composite CR (CRc = CR + Complete response with incomplete blood count recovery [CRi] + Complete response with incomplete platelet recovery [CRp]) rate. - Number of days alive and out of the hospital. - Progression-free survival (PFS). - Transfusion needs. - Health-related quality of life (QOL). - Duration of CR. - Safety.

SGI-110 for subcutaneous injection

Azacitidine
Sodium (2R,3S,5R)-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)-2-(hydroxymethyl)tetrahydrofuran-3-yl ((2

Injection
vial, diluent/ SC injection

100

Co-primary Endpoints
• CR rate based on modified International Working Group (IWG) 2003 AML Response Criteria.
• OS, defined as the number of days from randomization to death.
Secondary Endpoints
• CRc (CR+CRi+CRp) rate.
• Number of days alive and out of the hospital.
• PFS, defined as the number of days from randomization to disease progression or death, whichever occurs
first.
• Number of red blood cell (RBC) or platelet transfusions (units) over the duration of the study treatment.
• Health-related QOL by EQ-5D (consisting of the EQ-5D-5L descriptive system and the EQ Visual Analogue
Scale [EQ VAS]).
• Duration of CR, defined as the time from first CR to time of relapse.
• Incidence and severity of adverse events (AEs).
• 30- and 60-day all-cause early mortality.

Inclusion Criteria
Subjects must fulfill all of the following inclusion criteria.
1. Able to understand and comply with study procedures, and provides written informed consent before any
study-specific procedure.
2. Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia)
according to the 2008 World Health Organization (WHO) classification (bone marrow or peripheral blood
blast counts ≥20%).
3. Performance status (ECOG) of 0-3.
4. Adults with previously untreated AML except for hydroxyurea or corticosteroids. Prior hydroxyurea or
lenalidomide treatment for myelodysplastic syndrome (MDS) is allowed.
5. Unfit to receive or not considered candidates for intensive remission induction chemotherapy at time of
enrollment based on EITHER:
a. ≥75 years of age
OR
b. <75 years of age with at least 1 of the following:
i. Poor performance status (ECOG) score of 2-3.
ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:
1) Left ventricular ejection fraction (LVEF) ≤50%.
2) Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected.
3) Forced expiratory volume in 1 second (FEV1) ≤65% of expected.
4) Chronic stable angina or congestive heart failure controlled with medication.
iii. Liver transaminases >3 × upper limit of normal (ULN).
iv. Other contraindication(s) to anthracycline therapy (must be documented).
v. Other comorbidity the investigator judges incompatible with intensive remission induction
chemotherapy, which must be documented and approved by the study medical monitor before
randomization.
6. Creatinine clearance as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas
≥30 mL/min.
7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy
test at screening. Women of child-bearing potential and men with female partners of child-bearing potential
must agree to practice 2 highly effective contraceptive measures during the study and for at least 3 months
after completing treatment and must agree not to become pregnant or father a child while receiving treatment
with SGI-110 and for at least 3 months after completing treatment.

Exclusion Criteria
Subjects meeting any of the following exclusion criteria will be excluded from the study:
1. Candidate for intensive remission induction chemotherapy at the time of enrollment.
2. Candidate for best supportive care only, ie, not a candidate for any active therapy with the TC comparators.
3. Known extramedullary central nervous system (CNS) AML.
4. Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding
to endocrine therapy.
5. Prior treatment with decitabine or azacitidine.
6. Hypersensitivity to decitabine, azacitidine, cytarabine, SGI-110, or any of their excipients.
7. Treated with any investigational drug within 2 weeks of the first dose of study treatment.
8. Total serum bilirubin >2.5 × ULN, except for subjects with Gilbert's Syndrome for whom direct bilirubin is
<2.5 × ULN, or liver cirrhosis or chronic liver disease Childs-Pugh B or C.
9. Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
10. Known significant mental illness or other condition such as active alcohol or other substance abuse or
addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with
the protocol.
11. Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all
antibiotics; or advanced pulmonary disease requiring >2 liters per minute (LPM) oxygen.