SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction

Astex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Treatment Choice; Drug: SGI-110 (guadecitabine)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02348489

SGI-110-04

Details and patient eligibility

About

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.

Enrollment: 815 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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815 participants in 2 patient groups

SGI-110 (guadecitabine)

Experimental group

Description:

Guadecitabine 60 mg/m\^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Treatment:

Drug: SGI-110 (guadecitabine)

Treatment Choice

Active Comparator group

Description:

One of the following treatment regimens: 20 mg cytarabine administered subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m\^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m\^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.

Treatment:

Drug: Treatment Choice