Trial Outcomes & Findings for A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy (NCT NCT02993523)

Last Updated: 2025-08-19

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

443 participants

Primary outcome timeframe

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)

Results posted on

2025-08-19

Participant Flow

Participants were randomized in Group 1 per original protocol stratified by age (18 - \< 75, ≥ 75), and region (US, EU, Japan (JP), Rest of world (ROW)) and Group 2 during or after Amendment 1 stratified by age (18 - \< 75, ≥ 75), cytogenetic risk (intermediate, poor) and region (US, EU, China, JP, ROW).

Total of 443 participants were enrolled. 433 participants were randomized in Group 1 and Group 2 to receive placebo or venetoclax 100/200/400mg+azacitidine 75mg/m\^2. 10 participants in open-label China cohort received venetoclax 400 mg + azacitidine 75 mg/m\^2 up to data cut-off date: 01 December 2021. This study is ongoing.

Participant milestones

Participant milestones
Measure	Group 1: Placebo + Azacitidine 75 mg/m^2 Participants enrolled under original protocol received venetoclax-matching placebo, orally, once daily (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 1: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 Participants enrolled under original protocol received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Placebo + Azacitidine 75 mg/m^2 Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Overall Study STARTED	1	1	145	286	10
Overall Study COMPLETED	0	0	1	48	4
Overall Study NOT COMPLETED	1	1	144	238	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Placebo + Azacitidine 75 mg/m^2 Participants enrolled under original protocol received venetoclax-matching placebo, orally, once daily (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 1: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 Participants enrolled under original protocol received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Placebo + Azacitidine 75 mg/m^2 Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Overall Study Withdrew Consent	0	0	2	9	0
Overall Study Lost to Follow-up	0	0	3	6	0
Overall Study Death	1	1	138	222	6
Overall Study Reason not Specified	0	0	1	1	0

Baseline Characteristics

A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Placebo + Azacitidine 75 mg/m^2 n=1 Participants Participants enrolled under original protocol received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 1: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 n=1 Participants Participants enrolled under original protocol received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Placebo + Azacitidine 75 mg/m^2 n=145 Participants Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 n=286 Participants Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 n=10 Participants Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Total n=443 Participants Total of all reporting groups
Age, Continuous	61.0 years STANDARD_DEVIATION NA • n=93 Participants	65.0 years STANDARD_DEVIATION NA • n=4 Participants	75.1 years STANDARD_DEVIATION 5.70 • n=27 Participants	75.6 years STANDARD_DEVIATION 6.08 • n=483 Participants	70.2 years STANDARD_DEVIATION 7.44 • n=36 Participants	75.2 years STANDARD_DEVIATION 6.08 • n=10 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	0 Participants n=4 Participants	58 Participants n=27 Participants	114 Participants n=483 Participants	4 Participants n=36 Participants	177 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	1 Participants n=4 Participants	87 Participants n=27 Participants	172 Participants n=483 Participants	6 Participants n=36 Participants	266 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	33 Participants n=27 Participants	66 Participants n=483 Participants	10 Participants n=36 Participants	109 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	0 Participants n=36 Participants	6 Participants n=10 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	1 Participants n=4 Participants	109 Participants n=27 Participants	217 Participants n=483 Participants	0 Participants n=36 Participants	327 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: 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)

Population: Full Analysis Set included all Group 2 participants randomized by IVRS/IWRS (exclude the open-label China safety cohort).

Outcome measures

Outcome measures
Measure	Group 2: Placebo + Azacitidine 75 mg/m^2 n=145 Participants Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 n=286 Participants Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Overall Survival (OS)	9.6 months Interval 7.4 to 12.7	14.7 months Interval 12.1 to 18.7	—

PRIMARY outcome

Timeframe: From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)

Population: Full Analysis Set included all Group 2 participants randomized by IVRS/IWRS (exclude the open-label China safety cohort). Open-Label China Safety Cohort included participants who received at least one dose of venetoclax. Data is reported for Group 2 and Open-label China Cohort.

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.

Outcome measures

Outcome measures
Measure	Group 2: Placebo + Azacitidine 75 mg/m^2 n=145 Participants Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 n=286 Participants Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 n=10 Participants Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi) CR	17.9 percentage of participants Interval 12.1 to 25.2	38.8 percentage of participants Interval 33.1 to 44.7	60.0 percentage of participants Interval 26.2 to 87.8
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi) CRi	11.0 percentage of participants Interval 6.4 to 17.3	28.0 percentage of participants Interval 22.8 to 33.6	20.0 percentage of participants Interval 2.5 to 55.6

SECONDARY outcome

Timeframe: Measured up to 2 years after the last participant is randomized

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months after the first 225 participants are randomized

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured up to 2 years after the last participant is randomized

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured up to 2 years after the last participant is randomized

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured up to 2 years after the last participant is randomized

The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score

Outcome measures

Outcome data not reported

Adverse Events

Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2

Serious events: 111 serious events

Other events: 137 other events

Deaths: 140 deaths

Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2

Serious events: 242 serious events

Other events: 279 other events

Deaths: 226 deaths

Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2

Serious events: 7 serious events

Other events: 10 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

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Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
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