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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03069352
Recruitment Status : Active, not recruiting
First Posted : March 3, 2017
Results First Posted : February 28, 2020
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia (AML)
Interventions Drug: Placebo
Drug: Venetoclax
Drug: Cytarabine
Enrollment 211
Recruitment Details 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).
Pre-assignment Details 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).
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 68 143
Received Treatment 68 142
Completed [1] 56 103
Not Completed 12 40
Reason Not Completed
Ongoing             12             40
[1]
As of 15 August 2019
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC) Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 68 143 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 68 participants 143 participants 211 participants
76.0
(41.0 to 88.0)
76.0
(36.0 to 93.0)
76.0
(36.0 to 93.0)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 143 participants 211 participants
18 to < 65 years
9
  13.2%
11
   7.7%
20
   9.5%
65 to < 75 years
19
  27.9%
50
  35.0%
69
  32.7%
≥ 75 years
40
  58.8%
82
  57.3%
122
  57.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 143 participants 211 participants
Female
29
  42.6%
65
  45.5%
94
  44.5%
Male
39
  57.4%
78
  54.5%
117
  55.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 143 participants 211 participants
White
47
  69.1%
102
  71.3%
149
  70.6%
Black or African American
1
   1.5%
2
   1.4%
3
   1.4%
Asian
20
  29.4%
39
  27.3%
59
  28.0%
Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 143 participants 211 participants
United States
6
   8.8%
13
   9.1%
19
   9.0%
European Union
26
  38.2%
56
  39.2%
82
  38.9%
China
6
   8.8%
9
   6.3%
15
   7.1%
Japan
9
  13.2%
18
  12.6%
27
  12.8%
Rest of World
21
  30.9%
47
  32.9%
68
  32.2%
[1]
Measure Description: Rest of World includes Australia, Brazil, Canada, New Zealand, Puerto Rico, Russia, South Africa, South Korea, and Taiwan.
AML Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 143 participants 211 participants
De novo
45
  66.2%
85
  59.4%
130
  61.6%
Secondary
23
  33.8%
58
  40.6%
81
  38.4%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Median (95% Confidence Interval)
Unit of Measure: months
4.1
(3.1 to 8.8)
7.2
(5.6 to 10.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments [Not Specified]
Method Log Rank
Comments Log-rank test stratified by AML status (de novo, secondary) and age (18 – < 75, ≥ 75).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.749
Confidence Interval (2-Sided) 95%
0.524 to 1.071
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model, stratified by AML status (de novo, secondary) and age (18 – < 75, ≥ 75).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments [Not Specified]
Method Log Rank
Comments Unstratified analysis
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.743
Confidence Interval (2-Sided) 95%
0.521 to 1.061
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model.
2.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.2
(6.2 to 23.6)
47.6
(39.1 to 56.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh)
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.7
(7.3 to 25.4)
46.9
(38.5 to 55.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Initiation of Cycle 2
Hide Description

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.

Time Frame Cycle 1, 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.9
(0.4 to 10.2)
34.3
(26.5 to 42.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR + CRh) by Initiation of Cycle 2
Hide Description

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.

Time Frame Cycle 1, 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.4
(0.9 to 12.4)
30.8
(23.3 to 39.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Complete Remission
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.4
(2.4 to 16.3)
27.3
(20.2 to 35.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a
Hide Description 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.
Time Frame Baseline and Day 1 of Cycles 3, 5, 7, and 9
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data at baseline and each time point
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 60 127
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Cycle 3 Day 1 Number Analyzed 22 participants 69 participants
1.567  (1.855) -2.940  (1.093)
Cycle 5 Day 1 Number Analyzed 12 participants 40 participants
-0.336  (2.307) -5.259  (1.308)
Cycle 7 Day 1 Number Analyzed 12 participants 36 participants
-3.818  (2.314) -4.625  (1.354)
Cycle 9 day 1 Number Analyzed 7 participants 22 participants
-3.453  (2.811) -5.101  (1.606)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 3, Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.507
Confidence Interval (2-Sided) 95%
-8.60 to -0.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.068
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 5 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.923
Confidence Interval (2-Sided) 95%
-10.03 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.580
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 7 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.807
Confidence Interval (2-Sided) 95%
-5.98 to 4.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.609
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 9 day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.648
Confidence Interval (2-Sided) 95%
-7.94 to 4.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.176
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments A linear mixed effects regression model with a variable covariance structure was fitted to the longitudinal data (considering all time points) to test for differences between treatment arms.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments [Not Specified]
Method Linear Mixed Effects Regression Model
Comments Model included AML status (de novo vs. secondary), age (18–< 75 vs. ≥ 75), treatment arm, time, and treatment arm by time interaction as fixed factors
8.Secondary Outcome
Title Change From Baseline in Global Health Status / Quality of Life
Hide Description

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.

Time Frame Baseline and Day 1 of Cycles 3, 5, 7, and 9
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with available data at Baseline and each time point
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 59 127
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Cycle 3 Day 1 Number Analyzed 22 participants 69 participants
1.941  (4.126) 4.857  (2.413)
Cycle 5 Day 1 Number Analyzed 12 participants 40 participants
2.627  (5.047) 16.015  (2.853)
Cycle 7 Day 1 Number Analyzed 12 participants 36 participants
3.481  (5.337) 10.599  (3.092)
Cycle 9 day 1 Number Analyzed 7 participants 22 participants
6.918  (6.642) 13.299  (3.772)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 3 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.917
Confidence Interval (2-Sided) 95%
-6.23 to 12.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.617
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 5 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 13.388
Confidence Interval (2-Sided) 95%
2.18 to 24.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.659
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 7 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 7.119
Confidence Interval (2-Sided) 95%
-4.83 to 19.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.031
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments Cycle 9 Day 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 6.381
Confidence Interval (2-Sided) 95%
-8.49 to 21.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.511
Estimation Comments A linear mixed-effects regression model with a covariance structure including baseline score, stratification factors (age and AML status) treatment arm, visit, and treatment arm by visit interaction.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments A linear mixed effects regression model with a variable covariance structure was fitted to the longitudinal data (considering all time points) to test for differences between treatment arms.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments [Not Specified]
Method Linear Mixed Effects Regression Model
Comments Model included AML status (de novo vs. secondary), age (18-< 75 vs. ≥ 75), treatment arm, time, and treatment arm by time interaction as fixed factors
9.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Median (95% Confidence Interval)
Unit of Measure: months
2.0
(1.6 to 3.1)
4.7
(3.7 to 6.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments Log-rank test stratified by AML status (de novo, secondary) and age (18 - < 75, ≥ 75).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.583
Confidence Interval (2-Sided) 95%
0.416 to 0.817
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model, stratified by AML status (de novo, secondary) and age (18 - < 75, ≥ 75).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Log Rank
Comments Unstratified analysis
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.601
Confidence Interval (2-Sided) 95%
0.430 to 0.839
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model.
10.Secondary Outcome
Title Percentage of Participants With Post Baseline Red Blood Cell (RBC) Transfusion Independence
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.6
(9.5 to 28.8)
40.6
(32.4 to 49.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 22.9
Confidence Interval (2-Sided) 95%
10.8 to 35.0
Estimation Comments Treatment difference = Venetoclax - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With Post Baseline Platelet Transfusion Independence
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
32.4
(21.5 to 44.8)
47.6
(39.1 to 56.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 15.2
Confidence Interval (2-Sided) 95%
1.4 to 29.0
Estimation Comments Treatment difference = Venetoclax - Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With RBC Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants who were RBC transfusion-dependent at Baseline
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 53 104
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.1
(6.7 to 27.6)
37.5
(28.2 to 47.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment Difference
Estimated Value 22.4
Confidence Interval (2-Sided) 95%
9.0 to 35.8
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With Platelet Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis participants who were platelet transfusion dependent at Baseline
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 24 53
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.5
(2.7 to 32.4)
30.2
(18.3 to 44.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 17.7
Confidence Interval (2-Sided) 95%
-0.4 to 35.8
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) and Minimal Residual Disease (MRD) Response
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.5
(0.0 to 7.9)
5.6
(2.4 to 10.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) and Minimal Residual Disease (MRD) Response
Hide Description

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.

Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.5
(0.0 to 7.9)
5.6
(2.4 to 10.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test stratified by age (18 - < 75, ≥ 75) and AML status (de novo, secondary).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
16.Secondary Outcome
Title Overall Survival (OS) by Mutation Subgroups
Hide Description

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
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set; participants in each mutation subgroup
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Median (95% Confidence Interval)
Unit of Measure: months
IDH1/2 mutation Number Analyzed 12 participants 21 participants
9.0 [1] 
(2.2 to NA)
10.8 [1] 
(4.2 to NA)
FLT3 mutation Number Analyzed 9 participants 20 participants
9.8 [1] 
(0.9 to NA)
5.9
(1.6 to 10.9)
[1]
Could not be calculated due to the low number of events
17.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Mutation Subgroup
Hide Description

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
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants in each mutation subgroup
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Unit of Measure: percentage of participants
IDH1/2 mutation Number Analyzed 12 participants 21 participants
33.3 57.1
FLT3 mutation Number Analyzed 9 participants 20 participants
44.4 45.0
18.Secondary Outcome
Title Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) by Mutation Subgroup
Hide Description

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
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants in each mutation subgroup
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Measure Type: Number
Unit of Measure: percentage of participants
IDH1/2 mutation Number Analyzed 12 participants 21 participants
33.3 57.1
FLT3 mutation Number Analyzed 9 participants 20 participants
44.4 45.0
19.Post-Hoc Outcome
Title Overall Survival After an Additional 6-Months Follow-up
Hide Description 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description:
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 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 Number of Participants Analyzed 68 143
Median (95% Confidence Interval)
Unit of Measure: months
4.1
(3.1 to 8.1)
8.4
(5.9 to 10.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Log Rank
Comments Log-rank test stratified by AML status (de novo, secondary) and age (18 - < 75, ≥ 75).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.704
Confidence Interval (2-Sided) 95%
0.503 to 0.985
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model, stratified by AML status (de novo, secondary) and age (18 - < 75, ≥ 75).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo + Low Dose Cytarabine (LDAC), Venetoclax + Low Dose Cytarabine (LDAC)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments [Not Specified]
Method Log Rank
Comments Unstratified analysis
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.717
Confidence Interval (2-Sided) 95%
0.514 to 1.000
Estimation Comments The hazard ratio was estimated using the Cox proportional hazards model.
Time Frame All-cause mortality includes all deaths up to the data cut-off date of 15 August 2019; median time on study 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. Adverse events are reported from the first dose of study drug up to 30 days after the last dose, to the data cut-off date of 15 August 2019; median duration of treatment was 1.7 months (range: 0.1-20.2) in the placebo arm and 4.1 months (range: 0.0-23.5) in the venetoclax arm.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Hide Arm/Group Description 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 received venetoclax 600 mg orally once a day plus cytarabine 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.
All-Cause Mortality
Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Affected / at Risk (%) Affected / at Risk (%)
Total   54/68 (79.41%)      99/142 (69.72%)    
Hide Serious Adverse Events
Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/68 (61.76%)      95/142 (66.90%)    
Blood and lymphatic system disorders     
ANAEMIA  1  0/68 (0.00%)  0 4/142 (2.82%)  4
DISSEMINATED INTRAVASCULAR COAGULATION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
FEBRILE NEUTROPENIA  1  12/68 (17.65%)  14 24/142 (16.90%)  32
HYPERLEUKOCYTOSIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
LEUKOCYTOSIS  1  2/68 (2.94%)  2 1/142 (0.70%)  1
LEUKOPENIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
NEUTROPENIA  1  0/68 (0.00%)  0 4/142 (2.82%)  4
THROMBOCYTOPENIA  1  2/68 (2.94%)  2 7/142 (4.93%)  8
Cardiac disorders     
ATRIAL FIBRILLATION  1  1/68 (1.47%)  1 2/142 (1.41%)  2
CARDIAC ARREST  1  1/68 (1.47%)  1 0/142 (0.00%)  0
CARDIAC FAILURE  1  3/68 (4.41%)  3 1/142 (0.70%)  1
CARDIAC FAILURE ACUTE  1  1/68 (1.47%)  1 4/142 (2.82%)  5
CARDIAC FAILURE CONGESTIVE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
RIGHT VENTRICULAR FAILURE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Eye disorders     
CONJUNCTIVAL HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
EYELID HAEMATOMA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
EYELID OEDEMA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
RETINAL HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Gastrointestinal disorders     
DIARRHOEA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GASTRIC HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GASTRITIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GASTRITIS EROSIVE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GASTRITIS HAEMORRHAGIC  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GASTROINTESTINAL HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
HAEMATOCHEZIA  1  1/68 (1.47%)  2 0/142 (0.00%)  0
PANCREATITIS ACUTE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
SMALL INTESTINAL OBSTRUCTION  1  0/68 (0.00%)  0 1/142 (0.70%)  2
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/68 (0.00%)  0 2/142 (1.41%)  4
General disorders     
DEATH  1  1/68 (1.47%)  1 0/142 (0.00%)  0
GENERAL PHYSICAL HEALTH DETERIORATION  1  1/68 (1.47%)  1 1/142 (0.70%)  1
MULTIPLE ORGAN DYSFUNCTION SYNDROME  1  1/68 (1.47%)  1 1/142 (0.70%)  1
PYREXIA  1  5/68 (7.35%)  7 3/142 (2.11%)  3
SUDDEN DEATH  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Hepatobiliary disorders     
CHOLECYSTITIS ACUTE  1  0/68 (0.00%)  0 2/142 (1.41%)  2
HYPERBILIRUBINAEMIA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
Infections and infestations     
ABSCESS NECK  1  0/68 (0.00%)  0 1/142 (0.70%)  1
APPENDICITIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
ASPERGILLUS INFECTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
BACTERAEMIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
BACTERIAL SEPSIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
BRONCHOPULMONARY ASPERGILLOSIS  1  1/68 (1.47%)  1 1/142 (0.70%)  1
CANDIDA SEPSIS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
CELLULITIS  1  2/68 (2.94%)  2 4/142 (2.82%)  4
CLOSTRIDIAL INFECTION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
CLOSTRIDIUM DIFFICILE INFECTION  1  0/68 (0.00%)  0 2/142 (1.41%)  2
ENTEROCOCCAL INFECTION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
ESCHERICHIA BACTERAEMIA  1  1/68 (1.47%)  1 1/142 (0.70%)  1
ESCHERICHIA INFECTION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
ESCHERICHIA URINARY TRACT INFECTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
EXTERNAL EAR CELLULITIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
INFLUENZA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
KLEBSIELLA INFECTION  1  1/68 (1.47%)  1 1/142 (0.70%)  1
KLEBSIELLA SEPSIS  1  2/68 (2.94%)  2 0/142 (0.00%)  0
LIVER ABSCESS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
LOCALISED INFECTION  1  1/68 (1.47%)  2 0/142 (0.00%)  0
LUNG INFECTION  1  2/68 (2.94%)  2 4/142 (2.82%)  4
LUNG INFECTION PSEUDOMONAL  1  1/68 (1.47%)  1 0/142 (0.00%)  0
METAPNEUMOVIRUS INFECTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
MUCORMYCOSIS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
NASOPHARYNGITIS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
NEUTROPENIC SEPSIS  1  0/68 (0.00%)  0 3/142 (2.11%)  3
ORAL CANDIDIASIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
OROPHARYNGEAL CANDIDIASIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PAROTITIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PNEUMOCYSTIS JIROVECII PNEUMONIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PNEUMONIA  1  7/68 (10.29%)  7 20/142 (14.08%)  24
PNEUMONIA FUNGAL  1  0/68 (0.00%)  0 2/142 (1.41%)  2
PNEUMONIA STAPHYLOCOCCAL  1  1/68 (1.47%)  1 0/142 (0.00%)  0
PSEUDOMONAL BACTERAEMIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PSOAS ABSCESS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PULMONARY MYCOSIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
RESPIRATORY TRACT INFECTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
SEPSIS  1  4/68 (5.88%)  4 8/142 (5.63%)  8
SEPTIC SHOCK  1  4/68 (5.88%)  4 5/142 (3.52%)  5
SERRATIA BACTERAEMIA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
SKIN INFECTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
STAPHYLOCOCCAL BACTERAEMIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
STAPHYLOCOCCAL INFECTION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
STAPHYLOCOCCAL SEPSIS  1  2/68 (2.94%)  2 1/142 (0.70%)  1
SUBCUTANEOUS ABSCESS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
TONSILLITIS  1  0/68 (0.00%)  0 1/142 (0.70%)  1
URINARY TRACT INFECTION  1  0/68 (0.00%)  0 3/142 (2.11%)  4
VASCULAR DEVICE INFECTION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
Injury, poisoning and procedural complications     
FALL  1  0/68 (0.00%)  0 1/142 (0.70%)  1
HIP FRACTURE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
MEDICATION ERROR  1  0/68 (0.00%)  0 1/142 (0.70%)  1
TRAUMATIC HAEMOTHORAX  1  1/68 (1.47%)  1 0/142 (0.00%)  0
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  0/68 (0.00%)  0 1/142 (0.70%)  1
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GENERAL PHYSICAL CONDITION ABNORMAL  1  1/68 (1.47%)  1 0/142 (0.00%)  0
NEUTROPHIL COUNT DECREASED  1  0/68 (0.00%)  0 1/142 (0.70%)  4
PLATELET COUNT DECREASED  1  1/68 (1.47%)  1 0/142 (0.00%)  0
WHITE BLOOD CELL COUNT DECREASED  1  0/68 (0.00%)  0 1/142 (0.70%)  4
Metabolism and nutrition disorders     
DECREASED APPETITE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
GOUT  1  0/68 (0.00%)  0 1/142 (0.70%)  2
HYPONATRAEMIA  1  0/68 (0.00%)  0 1/142 (0.70%)  1
TUMOUR LYSIS SYNDROME  1  0/68 (0.00%)  0 2/142 (1.41%)  2
Musculoskeletal and connective tissue disorders     
MUSCULAR WEAKNESS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
TENDONITIS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
TUMOUR ASSOCIATED FEVER  1  2/68 (2.94%)  2 0/142 (0.00%)  0
Nervous system disorders     
CEREBRAL HAEMATOMA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
CEREBRAL HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
CEREBROVASCULAR ACCIDENT  1  0/68 (0.00%)  0 2/142 (1.41%)  2
DIZZINESS  1  1/68 (1.47%)  1 0/142 (0.00%)  0
HAEMORRHAGE INTRACRANIAL  1  1/68 (1.47%)  1 1/142 (0.70%)  1
LETHARGY  1  0/68 (0.00%)  0 1/142 (0.70%)  1
ORTHOSTATIC INTOLERANCE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PRESYNCOPE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
SEIZURE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
SYNCOPE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
TRANSIENT ISCHAEMIC ATTACK  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  0/68 (0.00%)  0 1/142 (0.70%)  1
URINARY RETENTION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Respiratory, thoracic and mediastinal disorders     
ACUTE RESPIRATORY FAILURE  1  2/68 (2.94%)  2 0/142 (0.00%)  0
DYSPNOEA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
LARYNGEAL OEDEMA  1  1/68 (1.47%)  1 0/142 (0.00%)  0
LUNG INFILTRATION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
PLEURAL EFFUSION  1  1/68 (1.47%)  1 0/142 (0.00%)  0
PULMONARY ALVEOLAR HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
PULMONARY HAEMORRHAGE  1  0/68 (0.00%)  0 1/142 (0.70%)  1
RESPIRATORY FAILURE  1  1/68 (1.47%)  1 2/142 (1.41%)  2
Skin and subcutaneous tissue disorders     
SKIN DISCOLOURATION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
Vascular disorders     
DEEP VEIN THROMBOSIS  1  0/68 (0.00%)  0 2/142 (1.41%)  2
HYPOTENSION  1  0/68 (0.00%)  0 1/142 (0.70%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Low Dose Cytarabine (LDAC) Venetoclax + Low Dose Cytarabine (LDAC)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   65/68 (95.59%)      135/142 (95.07%)    
Blood and lymphatic system disorders     
ANAEMIA  1  15/68 (22.06%)  17 37/142 (26.06%)  60
FEBRILE NEUTROPENIA  1  8/68 (11.76%)  11 22/142 (15.49%)  24
LEUKOPENIA  1  5/68 (7.35%)  6 13/142 (9.15%)  17
NEUTROPENIA  1  12/68 (17.65%)  14 65/142 (45.77%)  130
THROMBOCYTOPENIA  1  25/68 (36.76%)  37 58/142 (40.85%)  117
Gastrointestinal disorders     
ABDOMINAL PAIN  1  3/68 (4.41%)  3 17/142 (11.97%)  17
ABDOMINAL PAIN UPPER  1  2/68 (2.94%)  2 9/142 (6.34%)  11
CONSTIPATION  1  22/68 (32.35%)  25 29/142 (20.42%)  38
DIARRHOEA  1  12/68 (17.65%)  15 46/142 (32.39%)  70
DYSPEPSIA  1  2/68 (2.94%)  2 9/142 (6.34%)  11
NAUSEA  1  21/68 (30.88%)  27 61/142 (42.96%)  95
STOMATITIS  1  0/68 (0.00%)  0 14/142 (9.86%)  15
VOMITING  1  10/68 (14.71%)  10 41/142 (28.87%)  59
General disorders     
ASTHENIA  1  8/68 (11.76%)  10 17/142 (11.97%)  20
FATIGUE  1  10/68 (14.71%)  10 22/142 (15.49%)  27
MALAISE  1  4/68 (5.88%)  4 4/142 (2.82%)  8
OEDEMA PERIPHERAL  1  14/68 (20.59%)  15 20/142 (14.08%)  27
PYREXIA  1  8/68 (11.76%)  10 22/142 (15.49%)  26
Infections and infestations     
ORAL HERPES  1  1/68 (1.47%)  1 9/142 (6.34%)  9
PNEUMONIA  1  4/68 (5.88%)  6 11/142 (7.75%)  12
Injury, poisoning and procedural complications     
FALL  1  0/68 (0.00%)  0 13/142 (9.15%)  15
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  5/68 (7.35%)  5 9/142 (6.34%)  14
ASPARTATE AMINOTRANSFERASE INCREASED  1  4/68 (5.88%)  4 12/142 (8.45%)  15
BLOOD BILIRUBIN INCREASED  1  1/68 (1.47%)  1 16/142 (11.27%)  17
NEUTROPHIL COUNT DECREASED  1  3/68 (4.41%)  5 9/142 (6.34%)  13
PLATELET COUNT DECREASED  1  3/68 (4.41%)  7 8/142 (5.63%)  18
WEIGHT DECREASED  1  2/68 (2.94%)  3 14/142 (9.86%)  18
WHITE BLOOD CELL COUNT DECREASED  1  4/68 (5.88%)  8 9/142 (6.34%)  22
Metabolism and nutrition disorders     
DECREASED APPETITE  1  13/68 (19.12%)  14 30/142 (21.13%)  35
HYPERGLYCAEMIA  1  5/68 (7.35%)  5 6/142 (4.23%)  9
HYPERPHOSPHATAEMIA  1  3/68 (4.41%)  3 11/142 (7.75%)  12
HYPOALBUMINAEMIA  1  9/68 (13.24%)  11 9/142 (6.34%)  11
HYPOCALCAEMIA  1  8/68 (11.76%)  10 13/142 (9.15%)  14
HYPOKALAEMIA  1  17/68 (25.00%)  24 44/142 (30.99%)  63
HYPOMAGNESAEMIA  1  6/68 (8.82%)  6 13/142 (9.15%)  14
HYPONATRAEMIA  1  7/68 (10.29%)  7 8/142 (5.63%)  8
HYPOPHOSPHATAEMIA  1  4/68 (5.88%)  4 5/142 (3.52%)  7
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  2/68 (2.94%)  2 12/142 (8.45%)  12
BACK PAIN  1  5/68 (7.35%)  6 9/142 (6.34%)  9
Nervous system disorders     
DIZZINESS  1  1/68 (1.47%)  1 12/142 (8.45%)  14
HEADACHE  1  3/68 (4.41%)  3 20/142 (14.08%)  28
Psychiatric disorders     
CONFUSIONAL STATE  1  5/68 (7.35%)  5 3/142 (2.11%)  3
INSOMNIA  1  9/68 (13.24%)  9 20/142 (14.08%)  20
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  5/68 (7.35%)  6 6/142 (4.23%)  8
Respiratory, thoracic and mediastinal disorders     
COUGH  1  6/68 (8.82%)  7 14/142 (9.86%)  17
DYSPNOEA  1  4/68 (5.88%)  5 11/142 (7.75%)  14
EPISTAXIS  1  3/68 (4.41%)  3 15/142 (10.56%)  20
PLEURAL EFFUSION  1  4/68 (5.88%)  4 5/142 (3.52%)  5
Skin and subcutaneous tissue disorders     
ERYTHEMA  1  4/68 (5.88%)  4 7/142 (4.93%)  10
PRURITUS  1  3/68 (4.41%)  3 8/142 (5.63%)  8
RASH  1  5/68 (7.35%)  7 10/142 (7.04%)  13
Vascular disorders     
HYPERTENSION  1  7/68 (10.29%)  8 14/142 (9.86%)  14
HYPOTENSION  1  2/68 (2.94%)  3 13/142 (9.15%)  18
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03069352    
Other Study ID Numbers: M16-043
2016-003900-30 ( EudraCT Number )
First Submitted: February 28, 2017
First Posted: March 3, 2017
Results First Submitted: February 14, 2020
Results First Posted: February 28, 2020
Last Update Posted: February 28, 2020