Acute Myeloid Leukaemia (AML) is an aggressive and rare cancer of myeloid cells (a white blood cell responsible for fighting infections). Successful treatment of AML is dependent on what subtype of AML the participant has, and the age of the participant when diagnosed. Venetoclax is an experimental drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. This study is designed to see if adding venetoclax to azacitidine works better than azacitidine on its own. This is a Phase 3, randomized, double-blind (treatment is unknown to participants and doctors), placebo controlled study in patients with AML who are \>= 18 or more years old and have not been treated before. Participants who take part in this study should not be suitable for standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 180 hospitals globally and enroll approximately 400 participants. In this study, 2/3 of participants will receive venetoclax every day with azacitidine and the remaining 1/3 will receive placebo (dummy) tablets with azacitidine. Participants will continue to have study visits and receive treatment for as long as they are having a clinical benefit. The effect of the treatment on AML will be checked by taking blood, bone marrow, scans, measuring side effects and by completing health questionnaires. Blood and bone marrow tests will be completed to see why some people respond better than others. Additional blood tests will be completed for genetic factors and to see how long the drug remains in the body.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
443
Solution for subcutaneous or intravenous administration.
Tablet
Matching placebo tablet
City of Hope /ID# 154105
Duarte, California, United States
University of California, Los Angeles /ID# 154107
Los Angeles, California, United States
University of California, Davis Comprehensive Cancer Center /ID# 162725
Sacramento, California, United States
Emory Midtown Infectious Disease Clinic /ID# 162534
Atlanta, Georgia, United States
Northwestern University Feinberg School of Medicine /ID# 201133
Chicago, Illinois, United States
Overall Survival (OS)
OS is defined as the number of days from the date of randomization to the date of death. Log rank test was used to compare the OS distribution between two treatment arms. Cox regression was used to report the hazard ratio.
Time frame: From the study start up to death or alive or lost to follow-up (up to approximately 4.8 years; data cut off date: 1 December 2021)
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi)
CR and CRi was calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count \>10\^3/ microliter (mcL), platelets \>10\^5/mcL, red cell transfusion independence, and bone marrow with \<5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤10\^3/mcL or platelets ≤10\^5/mcL. Percentages are rounded off to whole number at the nearest decimal.
Time frame: From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)
Event-free Survival (EFS)
EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.
Time frame: Measured up to 2 years after the last participant is randomized
Global Health Status/Quality of Life (GHS/QoL)
Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
Time frame: Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit
Percentage of Participants Achieving Composite Complete Remission (CR or CRi)
This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count \> 10\^3/mcL, platelets \> 10\^5/mcL, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of \<= 10\^3/mcL or platelets \<= 10\^5/mcL.
Time frame: Up to 6 months after the first 225 participants are randomized
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)
A response of CRh is defined as Bone marrow with \<5% blasts, peripheral blood neutrophil count \>0.5\*10\^3/mcL and peripheral blood platelet count \>0.5\*10\^5/mcL.
Time frame: Measured up to 2 years after the last participant is randomized
Post Baseline Transfusion Independence Rate
Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.
Time frame: Measured up to 2 years after the last participant is randomized
Complete Remission (CR) Rate
The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.
Time frame: Measured up to 2 years after the last participant is randomized
Fatigue/Quality of Life (QoL)
Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score
Time frame: Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Chicago Medicine /ID# 154108
Chicago, Illinois, United States
Fort Wayne Medical Oncology /ID# 157190
Fort Wayne, Indiana, United States
Cotton-O'Neil Clinical Res Ctr /ID# 155136
Topeka, Kansas, United States
Norton Cancer Institute /ID# 154992
Louisville, Kentucky, United States
EMMC Cancer Care /ID# 154991
Brewer, Maine, United States
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