Clinical Trials List
Protocol NumberM16-043
NCT Number(ClinicalTrials.gov Identfier)NCT03069352
Completed
2017-06-01 - 2026-08-31
Phase III
Terminated4
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax Co-Administered With Low Dose Cytarabine Versus Low Dose Cytarabine in Treatment Naïve Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
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Trial Applicant
AbbVie
-
Sponsor
AbbVie
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Co-Principal Investigator
- Hui-Hua Hsiao 未分科
Audit
None
Co-Principal Investigator
- MING YAO Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- SHAN-CHI YU Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Wen-Chien Chou Division of Others -
- CHENG-HONG TSAI Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 蔡郁棻 Division of Hematology & Oncology
- 許瑞峰 Division of Hematology & Oncology
- Hui-Ching Wang Division of Hematology & Oncology
- Yi-Chang Liu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Acute Myeloid Leukemia
Objectives
Primary Objective:
To evaluate if venetoclax when co-administered with low dose cytarabine (LDAC) improves
overall survival (OS) versus LDAC and placebo, in treatment naïve subjects with acute myeloid leukemia (AML).
Secondary Objectives:
To evaluate if venetoclax when co-administered with LDAC improves composite complete
remission rate (complete remission + complete remission with incomplete blood count recovery, CR + CRi).
To evaluate if venetoclax when co-administered with LDAC improves event-free survival (EFS).
To evaluate if venetoclax when co-administered with LDAC improves the proportion of
subjects achieving a composite CR (CR + CRi) by the initiation of Cycle 2.
To evaluate if venetoclax when co-administered with LDAC reduces fatigue based on patient
reported outcome (PRO) assessment Patient Reported Outcomes Measurement Information
System (PROMIS), Fatigue Short Form (SF) 7a.
To evaluate if venetoclax when co-administered with LDAC improves subjects Global Health
Status/Quality of Life (GHS/QoL) based on the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
Test Drug
Venetoclax (ABT-199/GDC-0199)
Active Ingredient
Venetoclax (ABT-199/GDC-0199)
Dosage Form
tablet
Dosage
100 /50 /10
Endpoints
Primary Efficacy Endpoints:
Overall Survival (OS):
Overall survival will be defined as the number of days from the date of randomization to the date of
death. Subjects that have not died will be censored at the last known date to be alive.
Secondary Efficacy Endpoints:
Composite Complete Remission Rate:
The proportion of subjects with complete remission or complete remission with incomplete blood count
recovery (CR + CRi) will be calculated based on current IWG criteria for AML. Subjects who are
randomized but have no IWG defined disease assessment will be considered as non-responders for
CR + CRi rate.
Event-Free Survival (EFS):
EFS will be defined as the number of days from randomization to the date of progressive disease, relapse
of CR or CRi, treatment failure, or death from any cause. If a specified event does not occur, subjects
will be censored at the date of last disease assessment. Data for subjects without any disease
assessments performed after randomization will be censored at the date of randomization.
Composite Complete Remission Rate by Initiation of Cycle 2:
The proportion of subjects with complete remission or complete remission with incomplete blood count
recovery (CR + CRi) by the initiation of Cycle 2 will be calculated based on modified IWG criteria for
AML. Subjects who are randomized but have no IWG defined disease assessment by the initiation of
Cycle 2 will be considered as non-responders.
Pharmacokinetic:
An analysis of venetoclax plasma concentrations may be performed using a nonlinear mixed effect
population PK modeling approach.
Pharmacodynamic and Predictive Biomarker Analysis:
Exploratory research may be conducted to find biomarkers predictive of venetoclax activity. Peripheral
blood and bone marrow samples will be obtained at study specified time points. Biomarkers
(e.g., characterization of Bcl-2 family members and MRD status may be assessed to compare patient
responses in the two arms in order to identify markers that may be predictive of venetoclax activity.
Safety:
A safety analysis will be performed for all dosed subjects unless otherwise indicated. For the study as a
whole, AEs will be evaluated and summarized. Laboratory test results and vital signs will be explored
for trends and summarized as appropriate.
Overall Survival (OS):
Overall survival will be defined as the number of days from the date of randomization to the date of
death. Subjects that have not died will be censored at the last known date to be alive.
Secondary Efficacy Endpoints:
Composite Complete Remission Rate:
The proportion of subjects with complete remission or complete remission with incomplete blood count
recovery (CR + CRi) will be calculated based on current IWG criteria for AML. Subjects who are
randomized but have no IWG defined disease assessment will be considered as non-responders for
CR + CRi rate.
Event-Free Survival (EFS):
EFS will be defined as the number of days from randomization to the date of progressive disease, relapse
of CR or CRi, treatment failure, or death from any cause. If a specified event does not occur, subjects
will be censored at the date of last disease assessment. Data for subjects without any disease
assessments performed after randomization will be censored at the date of randomization.
Composite Complete Remission Rate by Initiation of Cycle 2:
The proportion of subjects with complete remission or complete remission with incomplete blood count
recovery (CR + CRi) by the initiation of Cycle 2 will be calculated based on modified IWG criteria for
AML. Subjects who are randomized but have no IWG defined disease assessment by the initiation of
Cycle 2 will be considered as non-responders.
Pharmacokinetic:
An analysis of venetoclax plasma concentrations may be performed using a nonlinear mixed effect
population PK modeling approach.
Pharmacodynamic and Predictive Biomarker Analysis:
Exploratory research may be conducted to find biomarkers predictive of venetoclax activity. Peripheral
blood and bone marrow samples will be obtained at study specified time points. Biomarkers
(e.g., characterization of Bcl-2 family members and MRD status may be assessed to compare patient
responses in the two arms in order to identify markers that may be predictive of venetoclax activity.
Safety:
A safety analysis will be performed for all dosed subjects unless otherwise indicated. For the study as a
whole, AEs will be evaluated and summarized. Laboratory test results and vital signs will be explored
for trends and summarized as appropriate.
Inclution Criteria
Main Inclusion:
A subject will be eligible for study participation if he/she meets the following criteria within 21 days
prior to randomization.
1. Subject must have histological confirmation of AML by WHO criteria, is ineligible for intensive
induction chemotherapy and either is:
≥ 75 years of age
OR
≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of fitness for
intensive induction chemotherapy:
o Eastern Cooperative Oncology Group (ECOG) Performance status of 2 – 3
o Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina
o DLCO ≤ 65% or FEV1 ≤ 65%
o Creatinine clearance ≥ 30 mL/min to < 45 ml/min
o Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN
o Other comorbidity that the physician judges to be incompatible with conventional
intensive chemotherapy which must be reviewed and approved by the study medical
monitor before study enrollment
2. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status:
of 0 to 2 for subjects ≥ 75 years of age
OR
of 0 to 3 for subjects between 18 to 74 years of age
3. Subject must have a projected life expectancy of at least 12 weeks.
4. Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min;
calculated by the Cockcroft Gault formula or measured by 24-hours urine collection.
5. Subject must have adequate liver function as demonstrated by:
aspartate aminotransferase (AST) ≤ 3.0 × ULN*
alanine aminotransferase (ALT) ≤ 3.0 × ULN*
bilirubin ≤ 1.5 × ULN*
o Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN
* Unless considered to be due to leukemic organ involvement.
6. Female subjects must be either postmenopausal defined as:
Age > 55 years with no menses for 12 or more months without an alternative medical cause.
Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause
AND an FSH level > 40 IU/L.
OR
Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
OR
A Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified
method of birth control starting at Study Day 1 through at least 180 days after the last dose of
study drug.
7. Male subjects who are sexually active, must agree, from Study Day 1 through at least 180 days after
the last dose of study drug, to practice the protocol specified contraception (Section 5.2.4). Male
subjects must agree to refrain from sperm donation from initial study drug administration through at
least 180 days after the last dose of study drug.
8. Females of childbearing potential must have negative results for pregnancy test performed:
At Screening with a serum sample obtained within 14 days prior to the first study drug
administration, and
Prior to dosing with urine sample obtained on Week 1 Day 1, if it has been > 7 days since
obtaining the serum pregnancy test results.
Subjects with borderline pregnancy tests at Screening must have a serum pregnancy test
≥ 3 days later to document continued lack of a positive result.
9 Subject must voluntarily sign and date an informed, approved by an Independent Ethics Committee
(IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
A subject will be eligible for study participation if he/she meets the following criteria within 21 days
prior to randomization.
1. Subject must have histological confirmation of AML by WHO criteria, is ineligible for intensive
induction chemotherapy and either is:
≥ 75 years of age
OR
≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of fitness for
intensive induction chemotherapy:
o Eastern Cooperative Oncology Group (ECOG) Performance status of 2 – 3
o Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina
o DLCO ≤ 65% or FEV1 ≤ 65%
o Creatinine clearance ≥ 30 mL/min to < 45 ml/min
o Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN
o Other comorbidity that the physician judges to be incompatible with conventional
intensive chemotherapy which must be reviewed and approved by the study medical
monitor before study enrollment
2. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status:
of 0 to 2 for subjects ≥ 75 years of age
OR
of 0 to 3 for subjects between 18 to 74 years of age
3. Subject must have a projected life expectancy of at least 12 weeks.
4. Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min;
calculated by the Cockcroft Gault formula or measured by 24-hours urine collection.
5. Subject must have adequate liver function as demonstrated by:
aspartate aminotransferase (AST) ≤ 3.0 × ULN*
alanine aminotransferase (ALT) ≤ 3.0 × ULN*
bilirubin ≤ 1.5 × ULN*
o Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN
* Unless considered to be due to leukemic organ involvement.
6. Female subjects must be either postmenopausal defined as:
Age > 55 years with no menses for 12 or more months without an alternative medical cause.
Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause
AND an FSH level > 40 IU/L.
OR
Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
OR
A Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified
method of birth control starting at Study Day 1 through at least 180 days after the last dose of
study drug.
7. Male subjects who are sexually active, must agree, from Study Day 1 through at least 180 days after
the last dose of study drug, to practice the protocol specified contraception (Section 5.2.4). Male
subjects must agree to refrain from sperm donation from initial study drug administration through at
least 180 days after the last dose of study drug.
8. Females of childbearing potential must have negative results for pregnancy test performed:
At Screening with a serum sample obtained within 14 days prior to the first study drug
administration, and
Prior to dosing with urine sample obtained on Week 1 Day 1, if it has been > 7 days since
obtaining the serum pregnancy test results.
Subjects with borderline pregnancy tests at Screening must have a serum pregnancy test
≥ 3 days later to document continued lack of a positive result.
9 Subject must voluntarily sign and date an informed, approved by an Independent Ethics Committee
(IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
Exclusion Criteria
Main Exclusion:
1. Subject has received any prior treatment for AML with the exception of hydroxyurea, allowed
through the first cycle of study treatment. Note: Prior treatment for Myelodysplastic Syndrome is
allowed except for use of cytarabine.
2. Subject had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential
thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without
BCR-ABL mutation.
3. Subjects that have acute promyelocytic leukemia (APL).
4. Subject has known CNS involvement with AML.
5. Subject has known HIV infection (due to potential drug-drug interactions between antiretroviral
medications and venetoclax).
6. Subject is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary
medications) are not excluded.
7. Subject has received strong or moderate CYP3A inducers 7 days prior to the initiation of study treatment.
8. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment
9. Subject has cardiovascular disability status of New York Heart Association Class > 2. Class 2 is
defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity
results in fatigue, palpitations, dyspnea, or angina pain.
10. Subject has chronic respiratory disease that requires continuous oxygen, or significant history of
renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular
disease, or any other medical condition that in the opinion of the investigator would adversely affect
his/her participating in this study.
11. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
12. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring
therapy (viral, bacterial or fungal).
13. Subject has a history of other malignancies prior to study entry, with the exception of:
Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
14. Subject has a white blood cell count > 25 × 109/L. (Note: Hydroxyurea administration or
leukapheresis is permitted to meet this criterion).
1. Subject has received any prior treatment for AML with the exception of hydroxyurea, allowed
through the first cycle of study treatment. Note: Prior treatment for Myelodysplastic Syndrome is
allowed except for use of cytarabine.
2. Subject had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential
thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without
BCR-ABL mutation.
3. Subjects that have acute promyelocytic leukemia (APL).
4. Subject has known CNS involvement with AML.
5. Subject has known HIV infection (due to potential drug-drug interactions between antiretroviral
medications and venetoclax).
6. Subject is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary
medications) are not excluded.
7. Subject has received strong or moderate CYP3A inducers 7 days prior to the initiation of study treatment.
8. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment
9. Subject has cardiovascular disability status of New York Heart Association Class > 2. Class 2 is
defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity
results in fatigue, palpitations, dyspnea, or angina pain.
10. Subject has chronic respiratory disease that requires continuous oxygen, or significant history of
renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular
disease, or any other medical condition that in the opinion of the investigator would adversely affect
his/her participating in this study.
11. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
12. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring
therapy (viral, bacterial or fungal).
13. Subject has a history of other malignancies prior to study entry, with the exception of:
Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
14. Subject has a white blood cell count > 25 × 109/L. (Note: Hydroxyurea administration or
leukapheresis is permitted to meet this criterion).
The Estimated Number of Participants
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Taiwan
20 participants
-
Global
211 participants
