SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Inductio
- Conditions
- Acute Myeloid Leukemia (AML)
- Registration Number
- JPRN-jRCT2080223017
- Lead Sponsor
- Otsuka Pharmaceutical Co., Ltd.
- Brief Summary
There was no statistically significant difference between guadecitabine and TC for the primary endpoints of CR rate or OS. Efficacy (CR and OS) and safety (Grade >=3 AEs) outcomes were most correlated with AUC of active metabolite decitabine exposure after SC guadecitabine administration. This trial did not demonstrate any effect of guadecitabine on ECG parameters.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 815
Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) according to 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. greater than or equal to 75 years of age OR
2. less than75 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:
a. Left ventricular ejection fraction (LVEF) less than or equal to 50%.
b. Lung diffusing capacity for carbon monoxide (DLCO) greater than or equal to 65% of expected.
c. Forced expiratory volume in 1 second (FEV1) less than or equal to 65% of expected.
d. Chronic stable angina or congestive heart failure controlled with medication.
iii. Liver transaminases more than 3 times 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 Cockroft-Gault (C-G) or other medically acceptable formulas greater than or equal to 30 mL/min.
-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 core binding factor (CBF) leukemia: t(8;21) or inv(16).
-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 greater than 2 liters per minute (LPM) oxygen.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>- Cmplete response (CR) <br>- Overall survival
- Secondary Outcome Measures
Name Time Method efficacy<br>- Composite CR<br>- Number of days alive and out of the hospital<br>- Progression-free survival (PFS) <br>- Number of red blood cell or platelet transfusions <br>- Health-related quality of life (QOL)<br>- Duration of CR