The purpose of this study in AML patients is to test whether vadastuximab talirine (SGN-CD33A; 33A) combined with either azacitidine or decitabine improves remission rates and extends overall survival as compared to placebo combined with either azacitidine or decitabine.
Hypomethylating agents (HMAs), such as decitabine or azacitidine, are considered a standard treatment for older patients with AML. The primary goals of this study are to test whether patients treated with an HMA (either decitabine or azacitidine) in combination with 33A will have better anti-tumor activity and/or survive longer than patients treated with an HMA in combination with placebo. Patients who meet eligibility criteria will be randomly assigned to one of two treatment groups: 1) 33A plus HMA (Experimental Arm); or 2) placebo plus HMA (Comparator Arm). In addition to evaluating survival and remission rates, the minimal residual disease (MRD)-negative remission rate, duration of remission, event free- and leukemia-free survival, and safety and tolerability will be compared between arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
240
33A, 10 mcg/kg, every 4 weeks via intravenous (IV) push
Volume equivalent to 10 mcg/kg, every 4 weeks via IV push
75 mg/m2 given subcutaneously (SC) or IV x 7 days, every 4 weeks
Overall Survival
Time from randomization to death due to any cause
Time frame: Up to 1.5 years
Composite Complete Remission (CRc) Rate
Number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) according to the modified response criteria for acute myeloid leukemia (AML) per Cheson 2003.
Time frame: Up to 1.5 years
Minimal Residual Disease (MRD)-Negative Composite Complete Remission Rate
Number of patients who achieve both remission (CR or CRi) and MRD-negative status
Time frame: Up to 1.5 years
Duration of Remission
Duration of remission is calculated from the first documentation of CR or CRi to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.
Time frame: Up to approximately 9.5 months
Event-free Survival
Event-free survival is calculated from the time of randomization to the first documentation of progression, relapse, or death, whichever comes first. Patients who do not have event (progression, relapse, or death) prior to analysis cutoff date are censored at the date of last response assessment. Patients who started another anticancer therapy before progression, relapse, or death are censored at the date of last response assessment prior to the start of new therapy. Patients who do not have response assessment post-baseline are censored at the date of randomization.
Time frame: Up to approximately 11.24 months
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20 mg/m2 given IV x 5 days, every 4 weeks
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
City of Hope National Medical Center
Duarte, California, United States
Pacific Hematology Oncology Associates
San Francisco, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Florida Cancer Specialists - South Region
Fort Myers, Florida, United States
Shands Cancer Center / University of Florida
Gainesville, Florida, United States
Memorial Cancer Institute
Miami, Florida, United States
Florida Center for Cellular Therapy / Blood and Marrow Transplant Center
Orlando, Florida, United States
Florida Cancer Specialists - North Region
St. Petersburg, Florida, United States
Northside Hospital
Atlanta, Georgia, United States
...and 118 more locations
Leukemia-free Survival
Leukemia-free survival is calculated from the first documentation of blast clearance (CR, CRi, mLFS) to the first documentation of disease relapse or death, whichever comes first. Patients who are in remission at the time of analysis cutoff are censored at the date of last response assessment. Patients who started another anticancer therapy before relapse or death are censored at the date of last response assessment prior to start of new therapy.
Time frame: Up to approximately 9.49 months
Type, Incidence, Severity, Seriousness, and Relatedness of Adverse Events
Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. SAE = serious adverse event. "Study treatment" in this data set refers to blinded study treatment.
Time frame: Up to 1.5 years
Incidence of Grade 3 or Higher Laboratory Abnormalities
Participants who experienced a laboratory grade increase to Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\], v4.03)
Time frame: Up to 1.5 years
Time to Complete Remission
Time to CR or CRi is the time from randomization to the first documentation of CR/CRi
Time frame: Up to 1.5 years
Mortality Rates at Day 30 and Day 60
30- and 60-day survival from date of randomization. Estimated using Kaplan-Meier method.
Time frame: Up to 60 days