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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02993523




Registration number
NCT02993523
Ethics application status
Date submitted
13/12/2016
Date registered
15/12/2016
Date last updated
28/02/2020

Titles & IDs
Public title
A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy
Scientific title
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
Secondary ID [1] 0 0
2016-001466-28
Secondary ID [2] 0 0
M15-656
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - Venetoclax
Treatment: Drugs - Placebo

Placebo Comparator: Placebo followed by Azacitidine - Matching Placebo for Venetoclax 400 mg orally QD on Days 1 - 28 plus Azacitidine 75 mg/m^2 SC or IV QD on Days 1 - 7 (28-day cycle)

Active Comparator: Venetoclax followed by Azacitidine - Venetoclax 400 mg orally every day (QD) on Days 1 - 28 plus Azacitidine 75 mg/m^2 subcutaneously (SC) or intravenous (IV) QD on Cycle Days 1 - 7 (28-day cycle)


Treatment: Drugs: Azacitidine
Solution for subcutaneous or intravenous administration

Treatment: Drugs: Venetoclax
Tablet

Treatment: Drugs: Placebo
Tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) - OS is defined as the number of days from the date of randomization to the date of death.
Timepoint [1] 0 0
Measured up to 2 years after the last participant is randomized
Primary outcome [2] 0 0
Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi) - This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/ microliter (mcL), platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.
Timepoint [2] 0 0
Measured up to 2 years after the last participant is randomized
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Measured up to 2 years after the last participant is randomized
Secondary outcome [2] 0 0
Global health status/quality of life (GHS/QoL) - Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
Timepoint [2] 0 0
Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit
Secondary outcome [3] 0 0
Percentage of participants achieving composite complete remission (CR or CRi) - This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.
Timepoint [3] 0 0
Up to 6 months after the first 225 participants are randomized
Secondary outcome [4] 0 0
Complete remission or complete remission with partial hematologic recovery rate (CR+CRh) - A response of CRh is defined as Bone marrow with <5% blasts, peripheral blood neutrophil count >0.5*10^3/mcL and peripheral blood platelet count >0.5*10^5/mcL.
Timepoint [4] 0 0
Measured up to 2 years after the last participant is randomized
Secondary outcome [5] 0 0
Post baseline transfusion independence rate - Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.
Timepoint [5] 0 0
Measured up to 2 years after the last participant is randomized
Secondary outcome [6] 0 0
Complete remission (CR) rate - The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.
Timepoint [6] 0 0
Measured up to 2 years after the last participant is randomized
Secondary outcome [7] 0 0
Fatigue/quality of life (QoL) - Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and Cancer Fatigue Short Form (SF) 7a global fatigue score
Timepoint [7] 0 0
Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit

Eligibility
Key inclusion criteria
- Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health
Organization (WHO) criteria, previously untreated and be ineligible for treatment with
a standard cytarabine and anthracycline induction regimen due age or comorbidities.

- Participant must be >= 18 years of age.

- Participant must have a projected life expectancy of at least 12 weeks.

- Participant must be considered ineligible for induction therapy defined by the
following:

a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of the
following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance
Status of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiring
treatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusing
capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in
1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v.
Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of
Normal (ULN); vi. Any other comorbidity that the physician judges to be incompatible
with intensive chemotherapy must be reviewed and approved by the AbbVie Therapeutic
Medical Director during screening and before study enrollment.

- Participant must have an ECOG Performance status:

1. 0 to 2 for Participants >= 75 years of age or

2. 0 to 3 for Participants >= 18 to 74 years of age.

- Participant must have adequate renal function as demonstrated by a creatinine >= 30
mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine
collection.

- Participant must have adequate liver function as demonstrated by:

1. aspartate aminotransferase (AST) <= 3.0 x ULN*

2. alanine aminotransferase (ALT) <= 3.0 x ULN*

3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ
involvement

i. Subjects who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

- Female participants must be either postmenopausal defined as:

1. Age > 55 years with no menses for 12 or more months without an alternative
medical cause.

2. Age = 55 years with no menses for 12 or more months without an alternative
medical cause AND an FSH level > 40 IU/L; or

3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy); or

4. 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.

- Male Participants who are sexually active, must ag