Trial Outcomes & Findings for A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia (NCT NCT02287233)

Last Updated: 2022-08-29

Results Overview

Dose-limiting toxicities (DLTs) were determined during cycle 1 of the dose-escalation phase and defined as Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 grade 4 (life threatening requiring urgent intervention) or 5 (resulted in death) toxicity, excluding adverse events commonly caused by AML (eg, neutropenia, fever). Hematologic DLT was defined as failure of platelet recovery to 25 × 10\^9/L or greater and absolute neutrophil count (ANC) to 0.5 × 10\^9/L or greater within 14 days of the last dose of venetoclax in the absence of residual AML.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

94 participants

Primary outcome timeframe

Up to 28 days (Cycle 1)

Results posted on

2022-08-29

Participant Flow

Previously untreated adults with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy were enrolled at nine study sites in the United States, Australia, Germany, and Italy between December 2014 and May 2017. The study consisted of a dose escalation phase (Phase 1) to determine the recommended Phase 2 dose (RPTD), and a dose expansion phase (Phase 2).

Participant milestones

Participant milestones
Measure	Phase 1: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Overall Study STARTED	8	10	76
Overall Study Treated	8	10	74
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	10	76

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Overall Study Adverse Event Not Related to Progression	1	2	10
Overall Study Adverse Event Related to Progression	0	2	8
Overall Study Physician Decision	1	2	4
Overall Study Progressive Disease with Death	0	0	10
Overall Study Progressive Disease Without Death	2	3	20
Overall Study Withdrawal by Subject	1	1	7
Overall Study Other	3	0	15
Overall Study Did Not Receive Treatment	0	0	2

Baseline Characteristics

A Study Evaluating Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Participants With Acute Myelogenous Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: 600 mg Venetoclax + LDAC n=8 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Phase 2: 600 mg Venetoclax + LDAC n=76 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.	Total n=94 Participants Total of all reporting groups
Age, Continuous	75.3 years STANDARD_DEVIATION 6.45 • n=5 Participants	74.4 years STANDARD_DEVIATION 3.72 • n=7 Participants	75.0 years STANDARD_DEVIATION 5.56 • n=5 Participants	74.9 years STANDARD_DEVIATION 5.43 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	27 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	49 Participants n=5 Participants	61 Participants n=4 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	10 Participants n=7 Participants	69 Participants n=5 Participants	87 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 28 days (Cycle 1)

Population: The DLT-evaluable population included participants who received at least 80% of planned Cycle 1 doses during the dose-escalation phase (Phase 1)

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=8 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Number of Participants With Dose-limiting Toxicities	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)

Population: Participants enrolled in Phase 1 who had at least one dose of venetoclax and had at least one reported pharmacokinetic (PK) sample concentration.

The highest concentration that a drug achieves in the blood after administration in a dosing interval.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax Cycle 1, Day 10 (Venetoclax with LDAC)	2.04 µg/mL Standard Deviation 1.45	2.26 µg/mL Standard Deviation 0.930	—
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax Cycle 1, Day 18 (Venetoclax alone)	2.92 µg/mL Standard Deviation 2.15	2.36 µg/mL Standard Deviation 1.22	—

PRIMARY outcome

Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)

Population: Participants enrolled in Phase 1 who had at least one dose of venetoclax and had at least one reported PK sample concentration

The time at which the maximum plasma concentration (Cmax) is observed.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax Cycle 1, Day 10 (Venetoclax with LDAC)	4.0 hours Interval 4.0 to 6.0	8.0 hours Interval 4.0 to 8.0	—
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax Cycle 1, Day 18 (Venetoclax Alone)	7.0 hours Interval 3.5 to 8.0	6.6 hours Interval 4.0 to 8.0	—

PRIMARY outcome

Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)

Population: Participants enrolled in Phase 1 who had at least one dose of venetoclax and had at least one reported PK sample concentration with available data at each time point

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax Cycle 1, Day 10 (Venetoclax with LDAC)	33.3 µg*h/mL Standard Deviation 27.5	33.4 µg*h/mL Standard Deviation 14.1	—
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax Cycle 1, Day 18 (Venetoclax Alone)	51.8 µg*h/mL Standard Deviation 36.9	35.4 µg*h/mL Standard Deviation 19.8	—

PRIMARY outcome

Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.

Population: Participants enrolled in Phase 1 who had at least one dose of cytarabine and had at least one reported PK sample concentration.

The highest concentration that a drug achieves in the blood after administration in a dosing interval.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine Cycle 1, Day 1 (LDAC Alone)	175 ng/mL Standard Deviation 47.0	174 ng/mL Standard Deviation 55.4	—
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine Cycle 1, Day 10 (LDAC with Venetoclax)	166 ng/mL Standard Deviation 32.1	175 ng/mL Standard Deviation 62.3	—

PRIMARY outcome

Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.

Population: Participants enrolled in Phase 1 who had at least one dose of cytarabine and had at least one reported PK sample concentration.

The time at which the maximum plasma concentration (Cmax) is observed.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine Cycle 1, Day 1 (LDAC Alone)	0.3 hours Interval 0.3 to 0.4	0.3 hours Interval 0.2 to 0.5	—
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine Cycle 1, Day 10 (LDAC with Venetoclax)	0.3 hours Interval 0.3 to 0.5	0.3 hours Interval 0.2 to 0.5	—

PRIMARY outcome

Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.

Population: Participants enrolled in Phase 1 who had at least one dose of cytarabine and had at least one reported PK sample concentration.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=7 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine Cycle 1, Day 1 (LDAC Alone)	194 ng*h/mL Standard Deviation 66.3	204 ng*h/mL Standard Deviation 62.9	—
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine Cycle 1, Day 10 (LDAC with Venetoclax)	231 ng*h/mL Standard Deviation 89.0	202 ng*h/mL Standard Deviation 54.9	—

PRIMARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg). Efficacy endpoints were pre-specified for Phase 2 only, and are reported for all participants who received the RPTD.

Overall response rate (ORR) is defined as the percentage of participants who achieved a complete remission (CR), complete remission with incomplete marrow recovery (CRi), or partial remission (PR) per the International Working Group (IWG) for AML response criteria, per investigator assessment. CR: absolute neutrophil count (ANC) ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRi: lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL. PR: all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Overall Response Rate	54.9 percentage of participants Interval 43.5 to 65.9	—	—

PRIMARY outcome

Timeframe: From first dose of study drug until 30 days after last dose of study drug; median (minimum, maximum) duration of treatment was 4.1 (0.2, 62.8) months overall.

Population: All enrolled participants who received at least one dose of study drug

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator rated the severity of each AE according to the CTCAE Version 4.0 and the following: Grade 1: The AE is transient and easily tolerated (mild). Grade 2: The AE causes discomfort and interrupts usual activities (moderate). Grade 3: The AE causes considerable interference with usual activities and may be incapacitating (moderate to severe). Grade 4: The AE is life threatening requiring urgent intervention. Grade 5: The AE resulted in death. The investigator assessed each event as either having a reasonable possibility or no reasonable possibility of being related to the use of study drug. Treatment-emergent events are defined as events that began or worsened in severity after the first dose of study drug.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=8 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC n=10 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC n=74 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any treatment-emergent adverse event (TEAE)	8 Participants	10 Participants	74 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 3 or 4	8 Participants	10 Participants	72 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 3 or above	8 Participants	10 Participants	72 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Venetoclax-related TEAE	8 Participants	9 Participants	66 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) LDAC-related TEAE	8 Participants	9 Participants	71 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to hospitalization	7 Participants	8 Participants	64 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to venetoclax discontinuation	3 Participants	5 Participants	24 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to LDAC discontinuation	3 Participants	5 Participants	26 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to venetoclax interruption	3 Participants	4 Participants	45 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to LDAC interruption	3 Participants	3 Participants	38 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to venetoclax reduction	0 Participants	1 Participants	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to LDAC reduction	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to death	1 Participants	4 Participants	15 Participants

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

Complete remission (CR) rate is defined as the percentage of participants who achieved a complete remission at any time point during the study per the modified IWG criteria for AML and investigator assessment. CR: absolute neutrophil count (ANC) ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. Participants who never achieved CR or had no IWG disease assessment were considered to be non-responders in the calculation of CR rate.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Complete Remission Rate	25.6 percentage of participants Interval 16.6 to 36.4	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

The percentage of participants who achieved a CR or CRi at any time point during the study per the modified IWG criteria for AML and investigator assessment. CR: absolute neutrophil count (ANC) ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRi: lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL Participants who never achieved CR or CRi or had no IWG disease assessment were considered to be non-responders in the calculation of CR + CRi rate.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate	53.7 percentage of participants Interval 42.3 to 64.7	—	—

SECONDARY outcome

Timeframe: Cycle 2, Day 1

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

The percentage of participants who achieved a CR or CRi by initiation of Cycle 2 of study treatment per the modified IWG criteria for AML and investigator assessment. CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRi: Lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL. Participants who never achieved CR or CRi or had no IWG disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRi rate by initiation of Cycle 2.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
CR Plus CRi Rate by Initiation of Cycle 2	28.0 percentage of participants Interval 18.7 to 39.1	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRi

The time to the first response of CR + CRi is defined as the time from the first date of study drug to the first response of CR or CRi per the IWG AML response criteria assessed by the investigator. CR: absolute neutrophil count (ANC) ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRi: lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=44 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Time to First Response of CR + CRi	1.4 months Interval 0.8 to 14.9	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRi

The time to the best response of CR + CRi is defined as the time from the first date of study drug to the best response of CR or CRi per the IWG AML response criteria assessed by the investigator. CR: absolute neutrophil count (ANC) ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRi: lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=44 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Time to Best Response of CR + CRi	2.8 months Interval 0.8 to 22.4	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

Complete remission with partial hematologic recovery is a derived response based on bone marrow blast and hematology laboratory values. CRh rate is defined as the percentage of participants who achieved CRh as the best response at any time point during the study. A participant achieved a CRh when meeting the following criteria: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10\^3 /µL and * Peripheral blood platelet count of \> 0.5 × 10\^5 /µL and * A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection. Participants who never achieved CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CRh rate.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Complete Remission With Partial Hematologic Recovery (CRh) Rate	20.7 percentage of participants Interval 12.6 to 31.1	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

CR + CRh rate is defined as the percentage of participants who achieved CR or CRh at any time point during the study. CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10\^3 /µL and * Peripheral blood platelet count of \> 0.5 × 10\^5 /µL and * A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection. Participants who never achieved CR/CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CR + CRh rate.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
CR Plus CRh Rate	46.3 percentage of participants Interval 35.3 to 57.7	—	—

SECONDARY outcome

Timeframe: Cycle 2, Day 1

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

CR + CRh rate by initiation of Cycle 2 is defined as the percentage of participants who achieved CR or CRh by initiation of Cycle 2 of study treatment. CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10\^3 /µL and * Peripheral blood platelet count of \> 0.5 × 10\^5 /µL and * A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection. Participants who never achieved CR/CRh or did not have disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRh rate by initiation of Cycle 2.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
CR Plus CRh Rate by Initiation of Cycle 2	30.5 percentage of participants Interval 20.8 to 41.6	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRh

The time to the first response of CR + CRh is defined as the time from the first date of study drug to the first response of CR or CRh. CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10\^3 /µL and * Peripheral blood platelet count of \> 0.5 × 10\^5 /µL and * A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=38 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Time to First Response of CR Plus CRh	1.0 months Interval 0.8 to 9.4	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRh

The time to the best response of CR + CRh is defined as the time from the first date of study drug to the best response of CR or CRh. CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with \< 5% blasts. CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria: * Bone marrow with \< 5% blasts and * Peripheral blood neutrophil count of \> 0.5 × 10\^3 /µL and * Peripheral blood platelet count of \> 0.5 × 10\^5 /µL and * A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=38 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Time to Best Response of CR Plus CRh	2.6 months Interval 0.8 to 22.4	—	—

SECONDARY outcome

Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.

Population: All enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

Best response determined using the IWG-AML response criteria during the course of treatment. * CR: ANC ≥ 10\^3 /µL, platelet counts ≥ 10\^5 /µL, RBC transfusion independence, and bone marrow with \< 5% blasts; * CRi: lack of morphologic evidence of leukemia (blasts \< 5%), and platelet counts \< 10\^5 /µL or ANC \< 10\^3 /µL; * PR: all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate; * MLFS: \< 5% blasts in an aspirate and/or bone marrow core sample; * RD: failure to achieve CR, CRi, PR; only including subjects surviving at least 7 days following completion of initial treatment cycle with evidence of persistent leukemia by blood and/or bone marrow examination; * PD: one or more of the following: ≥ 50% decrement from maximum response levels in neutrophils or platelets; a reduction in hemoglobin by at least 2 g/dL; or transfusion dependence not due to other toxicities and bone marrow blast ≥ 5%.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Best Response Based on IWG Criteria Complete Remission (CR)	21 Participants	—	—
Best Response Based on IWG Criteria Complete Remission with Incomplete Marrow Recovery (CRi)	23 Participants	—	—
Best Response Based on IWG Criteria Partial Remission (PR)	1 Participants	—	—
Best Response Based on IWG Criteria Morphologically Leukemia Free State (MLFS)	6 Participants	—	—
Best Response Based on IWG Criteria Resistant Disease (RD)	19 Participants	—	—
Best Response Based on IWG Criteria Disease Progression (PD)	4 Participants	—	—
Best Response Based on IWG Criteria Discontinued With No Response Data (DS)	8 Participants	—	—

SECONDARY outcome

Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR

Duration of CR is defined as the time from date that a participant achieved CR to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the duration of CR analysis.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=21 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Duration of Complete Response	14.8 months Interval 7.2 to Could not be estimated due to the low number of events	—	—

SECONDARY outcome

Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRi

Duration of CR + CRi is defined as the time from the date that a participant achieved CR or CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=44 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Duration of CR Plus CRi	9.8 months Interval 5.3 to 14.9	—	—

SECONDARY outcome

Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CRi

Duration of CRi is defined as the time from date that a participant achieved CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=23 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Duration of CRi	4.7 months Interval 2.6 to 5.6	—	—

SECONDARY outcome

Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) with a response of CR or CRh

Duration of CR + CRh is defined as the time from date that a participant achieved CR or CRh to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRh was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=38 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Duration of CR Plus CRh	11.0 months Interval 6.1 to 28.2	—	—

SECONDARY outcome

Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

Overall survival is defined as the time from the date of first dose to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study drug, or after the participant discontinued study drug. OS was estimated using Kaplan-Meier methodology. Participants who were still alive were censored at the analysis date.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Overall Survival (OS)	9.7 months Interval 5.7 to 14.0	—	—

SECONDARY outcome

Timeframe: From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg)

Post baseline transfusion independence rate was estimated as the percentage of participants who achieved transfusion independence during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days (≥ 56 days) with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier. Results are reported for participants who achieved both RBC and platelet transfusion independence and for participants who received RBC transfusion independence and platelet transfusion independence.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=82 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Post Baseline Transfusion Independence Rate RBC and platelet transfusion independence	45.1 percentage of participants Interval 34.1 to 56.5	—	—
Post Baseline Transfusion Independence Rate RBC transfusion independence	47.6 percentage of participants Interval 36.4 to 58.9	—	—
Post Baseline Transfusion Independence Rate Platelet transfusion independence	58.5 percentage of participants Interval 47.1 to 69.3	—	—

SECONDARY outcome

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) who received a RBC or platelet transfusion within 8 weeks prior to first dose (60), an RBC transfusion within 8 weeks prior to first dose (53) or a platelet transfusion within 8 weeks prior to first dose (23).

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=60 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline RBC and platelet transfusion independence	45.0 percentage of participants Interval 32.1 to 58.4	—	—
Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline RBC transfusion independence	45.3 percentage of participants Interval 31.6 to 59.6	—	—
Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline Platelet transfusion independence	60.9 percentage of participants Interval 38.5 to 80.3	—	—

SECONDARY outcome

Population: Enrolled participants who received venetoclax with LDAC at the recommended Phase 2 dose (600 mg) who achieved post-baseline RBC or platelet transfusion independence overall (50), RBC and platelet transfusion independence (37), RBC transfusion independence (39), or platelet transfusion independence (48).

The duration of transfusion independence is defined as the first time period that a participant received no RBC/platelet transfusions for at least 56 days during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.

Outcome measures

Outcome measures
Measure	Phase 1: 600 mg Venetoclax + LDAC n=50 Participants Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg (Day 2) and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received low-dose cytarabine (LDAC; 20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 1: 800 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 100 mg (Day 2) and increased up to 800 mg by Day 6. Beginning with Cycle 2, 800 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle.	Phase 2: 600 mg Venetoclax + LDAC Venetoclax was administered orally once daily (QD) on Days 2 through 28 of Cycle 1. Dosing started at 50 mg, and increased up to 600 mg by Day 6. Beginning with Cycle 2, 600 mg venetoclax was administered Days 1 through 28 of each 28-day cycle. Participants also received LDAC (20 mg/m²) administered by subcutaneous injection once daily on Days 1 to 10 of each cycle. Participants could continue receiving treatment until disease progression or until discontinuation criteria were met.
Duration of Post Baseline Transfusion Independence Duration of RBC and platelet transfusion independence	150 days Interval 56.0 to 1855.0	—	—
Duration of Post Baseline Transfusion Independence Duration of RBC transfusion independence	123 days Interval 56.0 to 1881.0	—	—
Duration of Post Baseline Transfusion Independence Duration of platelet transfusion independence	155.5 days Interval 56.0 to 1855.0	—	—

Adverse Events

Phase 1: 600 mg Venetoclax + LDAC

Serious events: 7 serious events

Other events: 8 other events

Deaths: 6 deaths

Phase 1: 800 mg Venetoclax + LDAC

Serious events: 9 serious events

Other events: 10 other events

Deaths: 10 deaths

Phase 2: 600 mg Venetoclax + LDAC

Serious events: 68 serious events

Other events: 74 other events

Deaths: 63 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