SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: SGI-110 (guadecitabine); Treatment Choice
Intervention description: Investigational medicinal product; Choice of one: cytarabine, decitabine, or azacitidine
Intervention MeSH terms: Guadecitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 815.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AML; Acute Myeloid Leukemia; SGI-110; DNA Hypomethylating Agen

Summary:

      To compare efficacy and safety between SGI-110 and Treatment Choice in adults with previously
      untreated AML who are not considered candidates for intensive remission induction
      chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic
        leukemia) according to World Health Organization (WHO) classification.

        Performance status (ECOG) of 0-3. Adults with previously untreated AML except for
        hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for
        myelodysplastic syndrome (MDS) is allowed.

        Not considered candidates for intensive remission induction chemotherapy at time of
        enrollment based on EITHER:

          1. ≥75 years of age OR

          2. <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.

        Creatinine clearance as estimated by the Cockcroft-Gault (C-G) or other medically
        acceptable formulas ≥30 mL/min.

        Exclusion Criteria:

        Candidate for intensive remission induction chemotherapy at the time of enrollment.

        Candidate for best supportive care only, ie, not a candidate for any active therapy with
        the TC comparators.

        Known extramedullary central nervous system (CNS) AML.

        Second malignancy currently requiring active therapy except breast or prostate cancer
        stable on or responding to endocrine therapy.

        Prior treatment with decitabine or azacitidine.

        Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.

        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.

        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.

        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.