Clinical Trials List
Protocol NumberM15-656
NCT Number(ClinicalTrials.gov Identfier)NCT02993523
2017-08-01 - 2023-05-31
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 in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy
-
Trial Applicant
AbbVie
-
Sponsor
AbbVie
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Hung Tsai Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chien-Yuan Chen Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- SHAN-CHI YU Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 許瑞峰 Division of Hematology & Oncology
- Hui-Hua Hsiao Division of Hematology & Oncology
- Hui-Ching Wang Division of Hematology & Oncology
- Yi-Chang Liu Division of Hematology & Oncology
- 蔡郁棻 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
Primary Objectives:
To evaluate if venetoclax in combination with azacitidine will improve overall survival (OS) and
composite complete remission rate (complete remission + complete remission with incomplete
marrow recovery; CR + CRi) versus placebo in combination with azacitidine, in treatment naïve
subjects with acute myeloid leukemia (AML).
Secondary Objectives:
To evaluate if venetoclax in combination with azacitidine will improve, event-free survival(EFS)
To evaluate if venetoclax in combination with azacitidine will improve the proportion of
subjects achieving composite complete remission (CR or CRi) by the initiation of Cycle 2.
To evaluate if venetoclax in combination with azacitidine reduces fatigue and improves global
health status/quality of life (GHS/QoL) based on patient reported outcome (PRO) assessments
(Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short
Form [SF] 7a and 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
Venetoclax 100 mg、50 mg及10 mg tablet
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.
Composite Complete Remission Rate:
The proportion of subjects with complete remission or complete remission with incomplete marrow
recovery (CR + CRi) will be calculated based on current IWG criteria for AML. Subjects who are
randomized but have no IWG 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
from 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.
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.
Composite Complete Remission Rate:
The proportion of subjects with complete remission or complete remission with incomplete marrow
recovery (CR + CRi) will be calculated based on current IWG criteria for AML. Subjects who are
randomized but have no IWG 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
from 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.
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 confirmation of AML by WHO criteria and be ineligible for treatment with a
standard cytarabine and anthracycline induction regimen due to age or co-morbidities.
2. Subject must be ≥ 18 years of age.
3. Subject must have a projected life expectancy of at least 12 weeks.
4. Subject must be considered ineligible for induction therapy defined by the following:
≥ 75 years of age;
OR
≥ 18 to 74 years of age with at least one of the following co-morbidities:
o ECOG Performance Status of 2 or 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 Any other comorbidity that the physician judges to be incompatible with intensive
chemotherapy must be reviewed and approved by the AbbVie TA MD before study
enrollment
5. 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 ≥ 18 to 74 years of age.
6. 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.
7. 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*
* Unless considered to be due to leukemic organ involvement
o Subjects who are < 75 years of age may have a bilirubin of ≤ 3.0 × ULN
8. 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
Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of
birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
9. Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after
the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree
to refrain from sperm donation from initial study drug administration through at least 90 days after
the last dose of study drug.
10. Female subjects 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 Cycle 1 Day 1, if it has been > 7 days since
obtaining the serum pregnancy test results.
11. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or studyspecific 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 confirmation of AML by WHO criteria and be ineligible for treatment with a
standard cytarabine and anthracycline induction regimen due to age or co-morbidities.
2. Subject must be ≥ 18 years of age.
3. Subject must have a projected life expectancy of at least 12 weeks.
4. Subject must be considered ineligible for induction therapy defined by the following:
≥ 75 years of age;
OR
≥ 18 to 74 years of age with at least one of the following co-morbidities:
o ECOG Performance Status of 2 or 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 Any other comorbidity that the physician judges to be incompatible with intensive
chemotherapy must be reviewed and approved by the AbbVie TA MD before study
enrollment
5. 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 ≥ 18 to 74 years of age.
6. 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.
7. 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*
* Unless considered to be due to leukemic organ involvement
o Subjects who are < 75 years of age may have a bilirubin of ≤ 3.0 × ULN
8. 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
Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of
birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
9. Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after
the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree
to refrain from sperm donation from initial study drug administration through at least 90 days after
the last dose of study drug.
10. Female subjects 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 Cycle 1 Day 1, if it has been > 7 days since
obtaining the serum pregnancy test results.
11. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or studyspecific procedures.
Exclusion Criteria
Main Exclusion:
1. Subject has received treatment with the following:
A hypomethylating agent and/or any chemo-therapeutic agent for Myelodysplastic syndrome(MDS).
CAR-T cell therapy.
Experimental therapies for MDS or AML.
2. Subject has history of myeloproliferative neoplasm [MPN].
3. Subject has:
Favorable risk cytogenetics such as t(8;21), inv(16), t(16;16) or t(15;17) as per the NCCN
Guidelines Version 2, 2016 for Acute Myeloid Leukemia.
4. Subject has acute promyelocytic leukemia
5. Subject has known active CNS involvement with AML.
6. Subject is known to be positive for HIV (HIV testing is not required.)
7. Subject is known to be positive for hepatitis B or C infection with the exception of those with an
undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with
serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
8. Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of
study treatment.
9. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
10. Subject has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is
defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity
results in fatigue, palpitations, dyspnea, or anginal pain.
11. 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.
12. Subject has a malabsorption syndrome or other condition that precludes enteral route of
administration.
13. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring
therapy (viral, bacterial or fungal).
14. Subject has a history of other malignancies within 2 years 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.
15. Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)
1. Subject has received treatment with the following:
A hypomethylating agent and/or any chemo-therapeutic agent for Myelodysplastic syndrome(MDS).
CAR-T cell therapy.
Experimental therapies for MDS or AML.
2. Subject has history of myeloproliferative neoplasm [MPN].
3. Subject has:
Favorable risk cytogenetics such as t(8;21), inv(16), t(16;16) or t(15;17) as per the NCCN
Guidelines Version 2, 2016 for Acute Myeloid Leukemia.
4. Subject has acute promyelocytic leukemia
5. Subject has known active CNS involvement with AML.
6. Subject is known to be positive for HIV (HIV testing is not required.)
7. Subject is known to be positive for hepatitis B or C infection with the exception of those with an
undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with
serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
8. Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of
study treatment.
9. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
10. Subject has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is
defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity
results in fatigue, palpitations, dyspnea, or anginal pain.
11. 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.
12. Subject has a malabsorption syndrome or other condition that precludes enteral route of
administration.
13. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring
therapy (viral, bacterial or fungal).
14. Subject has a history of other malignancies within 2 years 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.
15. Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)
The Estimated Number of Participants
-
Taiwan
28 participants
-
Global
412 participants
