Trial Outcomes & Findings for A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy (NCT NCT03069352)

NCT ID: NCT03069352

Last Updated: 2025-09-30

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

From randomization until the primary analysis cut-off date of February 15 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.

Results posted on

2025-09-30

Participant Flow

Participants were enrolled at 76 sites globally. The study is currently ongoing; the results reported below include the primary analysis for efficacy which was conducted after 133 deaths occurred (data cut-off date of 15 February 2019), and an unplanned 6-month follow-up update for overall survival and safety (15 August 2019 cut-off date).

Participants with acute myeloid leukemia (AML) were randomized to one of two treatment arms in a 1:2 ratio (placebo + low-dose cytarabine \[LDAC\] or venetoclax + LDAC). Randomization was stratified by AML status (secondary, de novo), age (18 - \< 75, ≥ 75) and region (United States \[US\], European Union \[EU\], China, Japan, rest of world).

Participant milestones

Participant milestones
Measure	Placebo + Low Dose Cytarabine (LDAC) Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle. Participants continued treatment until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation were met.	Venetoclax + Low Dose Cytarabine (LDAC) Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle. Participants continued treatment until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation were met.
Overall Study STARTED	68	143
Overall Study Received Treatment	68	142
Overall Study COMPLETED	56	103
Overall Study NOT COMPLETED	12	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Low Dose Cytarabine (LDAC) Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle. Participants continued treatment until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation were met.	Venetoclax + Low Dose Cytarabine (LDAC) Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle. Participants continued treatment until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation were met.
Overall Study Ongoing	12	40

Baseline Characteristics

A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Total n=211 Participants Total of all reporting groups
Age, Continuous	76.0 years n=5 Participants	76.0 years n=7 Participants	76.0 years n=5 Participants
Age, Customized 18 to < 65 years	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized 65 to < 75 years	19 Participants n=5 Participants	50 Participants n=7 Participants	69 Participants n=5 Participants
Age, Customized ≥ 75 years	40 Participants n=5 Participants	82 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	65 Participants n=7 Participants	94 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	78 Participants n=7 Participants	117 Participants n=5 Participants
Race/Ethnicity, Customized White	47 Participants n=5 Participants	102 Participants n=7 Participants	149 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	20 Participants n=5 Participants	39 Participants n=7 Participants	59 Participants n=5 Participants
Region United States	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Region European Union	26 Participants n=5 Participants	56 Participants n=7 Participants	82 Participants n=5 Participants
Region China	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Region Japan	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants
Region Rest of World	21 Participants n=5 Participants	47 Participants n=7 Participants	68 Participants n=5 Participants
AML Status De novo	45 Participants n=5 Participants	85 Participants n=7 Participants	130 Participants n=5 Participants
AML Status Secondary	23 Participants n=5 Participants	58 Participants n=7 Participants	81 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the primary analysis cut-off date of February 15 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.

Population: The full analysis set included all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Overall Survival (OS)	4.1 months Interval 3.1 to 8.8	7.2 months Interval 5.6 to 10.1

SECONDARY outcome

Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.

Population: Full analysis set

The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML: CR: No morphologic evidence of AML and absolute neutrophil count (ANC) ≥ 10³/μL (1,000/μL), platelets ≥ 10⁵/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia \< 10³/μL or thrombocytopenia \< 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, the CRi criteria are met. Participants who had no IWG disease assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)	13.2 percentage of participants Interval 6.2 to 23.6	47.6 percentage of participants Interval 39.1 to 56.1

SECONDARY outcome

Population: Full analysis set

The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) at any time point during the study assessed by the investigator. CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is a derived response based on bone marrow blast and hematology lab values, achieved when the following criteria are met: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10³/μL and * Peripheral blood platelet count of \> 0.5 × 10⁵/μL and * A 1 week platelet transfusion-free period prior to the hematology lab collection. Participants with no disease assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh)	14.7 percentage of participants Interval 7.3 to 25.4	46.9 percentage of participants Interval 38.5 to 55.4

SECONDARY outcome

Timeframe: Cycle 1, 28 days

Population: Full analysis set

The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) before initiation of Cycle 2, assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML: CR: No morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red cell transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia \< 10³/μL or thrombocytopenia \< 10⁵/μL. If all criteria for CR are met except for RBC transfusion independence, CRi criteria are met. Participants who had no IWG disease assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Initiation of Cycle 2	2.9 percentage of participants Interval 0.4 to 10.2	34.3 percentage of participants Interval 26.5 to 42.7

SECONDARY outcome

Timeframe: Cycle 1, 28 days

Population: Full analysis set

The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) before initiation of Cycle 2 assessed by the investigator. CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is a derived response based on bone marrow blast and hematology lab values, achieved when when the following criteria are met: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10³/μL and * Peripheral blood platelet count of \> 0.5 × 10⁵/μL and * A 1-week platelet transfusion-free period prior to the hematology lab collection. Participants with no disease assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR + CRh) by Initiation of Cycle 2	4.4 percentage of participants Interval 0.9 to 12.4	30.8 percentage of participants Interval 23.3 to 39.0

SECONDARY outcome

Population: Full analysis set

The complete remission rate is defined as the percentage of participants with complete remission (CR) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML. CR is defined as no morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. Participants who had no IWG disease assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission	7.4 percentage of participants Interval 2.4 to 16.3	27.3 percentage of participants Interval 20.2 to 35.3

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 3, 5, 7, and 9

Population: Full analysis set with available data at baseline and each time point

PROMIS Fatigue SF 7a is a seven-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always. The PROMIS Fatigue 7a score is calculated as a T-score, which is a standardized score with a mean of 50 (based on the average for the United States general population) and a standard deviation (SD) of 10. Higher scores indicate higher levels of fatigue. A decrease in score (negative change from Baseline) indicates improvement in fatigue; the minimum important difference used in this study was 3 points.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=60 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=127 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Cycle 3 Day 1	1.567 score on a scale Standard Error 1.855	-2.940 score on a scale Standard Error 1.093
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Cycle 5 Day 1	-0.336 score on a scale Standard Error 2.307	-5.259 score on a scale Standard Error 1.308
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Cycle 7 Day 1	-3.818 score on a scale Standard Error 2.314	-4.625 score on a scale Standard Error 1.354
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Cycle 9 day 1	-3.453 score on a scale Standard Error 2.811	-5.101 score on a scale Standard Error 1.606

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 3, 5, 7, and 9

Population: Full analysis set with available data at Baseline and each time point

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) consists of a Global Health Status/Quality of Life (GHS/QoL) scale, a Financial Difficulties scale, 5 functional scales (Cognitive, Social, Physical, Emotional, and Role Functioning), and 8 symptom scales/items (Fatigue, Insomnia, Appetite Loss, Pain, Constipation, Diarrhea, Dyspnea, and Nausea and Vomiting). The GHS/QoL scale includes 2 questions in which participants were asked to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The 2 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=59 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=127 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Change From Baseline in Global Health Status / Quality of Life Cycle 3 Day 1	1.941 scores on a scale Standard Error 4.126	4.857 scores on a scale Standard Error 2.413
Change From Baseline in Global Health Status / Quality of Life Cycle 5 Day 1	2.627 scores on a scale Standard Error 5.047	16.015 scores on a scale Standard Error 2.853
Change From Baseline in Global Health Status / Quality of Life Cycle 7 Day 1	3.481 scores on a scale Standard Error 5.337	10.599 scores on a scale Standard Error 3.092
Change From Baseline in Global Health Status / Quality of Life Cycle 9 day 1	6.918 scores on a scale Standard Error 6.642	13.299 scores on a scale Standard Error 3.772

SECONDARY outcome

Timeframe: From randomization until the primary analysis cut-off date of February 15, 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.

Population: Full analysis set

Event-free survival is defined as the time from randomization to the date of progressive disease (PD), confirmed morphologic relapse from CR or CRi, treatment failure (failure to achieve CR, CRi or morphologic leukemia free state (MLFS) after at least 6 cycles of study treatment), or death from any cause, assessed by the investigator according to the modified IWG criteria. PD: * \> 50% increase in marrow blasts (minimum 15% increase required if blasts \< 30% at baseline); or persistent marrow blast \> 70% for ≥ 3 months; without at least a 100% improvement in ANC to an absolute level \> 0.5 × 10⁹/L, and/or platelets to \> 50 × 10⁹/L non-transfused; or * 50% increase in peripheral blasts to \> 25 × 10⁹/L; or * New extramedullary disease Participants with no events prior to the cut-off date were censored at their last assessment date; participants with no events prior to post-treatment therapy initiated before the cut-off date were censored on the start date of post-treatment therapy.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Event-free Survival (EFS)	2.0 months Interval 1.6 to 3.1	4.7 months Interval 3.7 to 6.4

SECONDARY outcome

Timeframe: From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.

Population: Full analysis set

The post baseline red blood cell (RBC) transfusion independence rate was calculated as the percentage of participants who achieved RBC transfusion independence post baseline. RBC transfusion independence is defined as a period of at least 56 consecutive days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Post Baseline Red Blood Cell (RBC) Transfusion Independence	17.6 percentage of participants Interval 9.5 to 28.8	40.6 percentage of participants Interval 32.4 to 49.1

SECONDARY outcome

Population: Full analysis set

The post baseline platelet transfusion independence rate was calculated as the percentage of participants who achieved platelet transfusion independence post Baseline. Platelet transfusion independence is defined as a period of at least 56 consecutive days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut--off date, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Post Baseline Platelet Transfusion Independence	32.4 percentage of participants Interval 21.5 to 44.8	47.6 percentage of participants Interval 39.1 to 56.1

SECONDARY outcome

Population: Full analysis set participants who were RBC transfusion-dependent at Baseline

The rate of conversion was calculated as the percentage of participants who were post-baseline RBC transfusion independent among participants who had an RBC transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). RBC transfusion independence is defined as a period of at least 56 days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=53 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=104 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With RBC Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline	15.1 percentage of participants Interval 6.7 to 27.6	37.5 percentage of participants Interval 28.2 to 47.5

SECONDARY outcome

Population: Full analysis participants who were platelet transfusion dependent at Baseline

The rate of conversion was calculated as the percentage of participants who were post-baseline platelet transfusion independent among participants who had a platelet transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). Platelet transfusion independence is defined as a period of at least 56 days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=24 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=53 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Platelet Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline	12.5 percentage of participants Interval 2.7 to 32.4	30.2 percentage of participants Interval 18.3 to 44.3

SECONDARY outcome

Population: Full analysis set

The percentage of participants with complete remission or complete remission with incomplete blood count recovery AND minimal residual disease (MRD) as assessed by the investigator. Response was based on the modified IWG response criteria for AML: CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell (RBC) transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia \< 10³/μL or thrombocytopenia \< 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria are met. MRD response (at lowest-point MRD value) was defined as having less than 10-³ residual blasts per leukocyte measured in the bone marrow, per European LeukemiaNet (ELN) recommendations. Participants who had no disease or MRD assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) and Minimal Residual Disease (MRD) Response	1.5 percentage of participants Interval 0.0 to 7.9	5.6 percentage of participants Interval 2.4 to 10.7

SECONDARY outcome

Population: Full analysis set

The percentage of participants with complete remission or complete remission with partial hematologic recovery (CRh) AND MRD response as assessed by the investigator. CR is defined according to the modified IWG response criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is achieved when the following criteria are met: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10³/μL and * Peripheral blood platelet count of \> 0.5 × 10⁵/μL and * A 1 week platelet transfusion-free period prior to the hematology lab collection. MRD response (at lowest-point MRD value) was defined as less than 10-³ residual blasts per leukocyte measured in the bone marrow, per ELN recommendations. Participants who had no disease or MRD assessments were considered to be non-responders.

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) and Minimal Residual Disease (MRD) Response	1.5 percentage of participants Interval 0.0 to 7.9	5.6 percentage of participants Interval 2.4 to 10.7

SECONDARY outcome

Population: The full analysis set; participants in each mutation subgroup

Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology. Overall survival was analyzed in participants with the following molecular markers: * Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation * FMS (Feline McDonough Sarcoma)-like tyrosine kinase 3 (FLT3) mutation

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Overall Survival (OS) by Mutation Subgroups IDH1/2 mutation	9.0 months Interval 2.2 to Could not be calculated due to the low number of events	10.8 months Interval 4.2 to Could not be calculated due to the low number of events
Overall Survival (OS) by Mutation Subgroups FLT3 mutation	9.8 months Interval 0.9 to Could not be calculated due to the low number of events	5.9 months Interval 1.6 to 10.9

SECONDARY outcome

Population: Full analysis set participants in each mutation subgroup

Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML: CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRi: All criteria as CR except for residual neutropenia \< 10³/μL or thrombocytopenia \< 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria is met. Participants who had no IWG disease assessments were considered to be non-responders. Response was analyzed in participants with the following mutations: * Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation * FMS-like tyrosine kinase 3 (FLT3) mutation

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Mutation Subgroup IDH1/2 mutation	33.3 percentage of participants	57.1 percentage of participants
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Mutation Subgroup FLT3 mutation	44.4 percentage of participants	45.0 percentage of participants

SECONDARY outcome

Population: Full analysis set participants in each mutation subgroup

The percentage of participants who achieved a complete remission or complete remission with partial hematologic recovery assessed by the investigator for participants with the following mutations: * Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation * FMS-like tyrosine kinase 3 (FLT3) mutation CR is defined according to the modified IWG criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, bone marrow with \< 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRh is achieved when the following criteria are met: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count \> 0.5 × 10³/μL and * Peripheral blood platelet count \> 0.5 × 10⁵/μL and * A 1 week platelet transfusion-free period prior to hematology lab collection. Participants with no disease assessments were considered non-responders

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) by Mutation Subgroup IDH1/2 mutation	33.3 percentage of participants	57.1 percentage of participants
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) by Mutation Subgroup FLT3 mutation	44.4 percentage of participants	45.0 percentage of participants

POST_HOC outcome

Timeframe: From randomization until the 6-month follow-up analysis cut-off date of August 15, 2019; the median follow-up time was 17.7 months (range: 0.2-20.8) in the placebo arm and 17.5 months (range: 0.1-23.5) in the venetoclax arm.

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo + Low Dose Cytarabine (LDAC) n=68 Participants Participants received matching placebo to venetoclax orally once a day (QD) plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.	Venetoclax + Low Dose Cytarabine (LDAC) n=143 Participants Participants received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
Overall Survival After an Additional 6-Months Follow-up	4.1 months Interval 3.1 to 8.1	8.4 months Interval 5.9 to 10.1

Adverse Events

Placebo + Low Dose Cytarabine (LDAC)

Serious events: 42 serious events

Other events: 65 other events

Deaths: 54 deaths

Venetoclax + Low Dose Cytarabine (LDAC)

Serious events: 95 serious events

Other events: 135 other events

Deaths: 99 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

Results disclosure agreements

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.
Publication restrictions are in place

Restriction type: OTHER