Back to resultsA Study of the Effectiveness of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in Patients With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy
Primary Purpose
Acute Myeloid Leukemia (AML), Cancer
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Venetoclax
Azacitidine
Decitabine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Acute Myeloid Leukemia (AML), Cancer, Treatment-naïve, Venetoclax, Azacitidine, Decitabine, Outpatient setting
Eligibility Criteria
Inclusion Criteria:
- Participant has confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria.
- Participant is deemed by the investigator to be an appropriate candidate for outpatient ramp-up of venetoclax.
- Participant is not eligible to receive treatment with standard cytarabine and anthracycline induction regimens.
- Participant has not received prior treatment for AML (treatment naïve) with the exception of hydroxyurea.
- Participant has no evidence of spontaneous tumor lysis syndrome (TLS) at Screening.
- Participant can have progressed from myelodysplastic syndrome (MDS) or be considered to have secondary AML and could have been treated with growth factors or other agents with the exception of hypomethylating agents.
- Participant has adequate kidney, liver and hematology laboratory values as detailed in the protocol.
- Has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 3.
Exclusion Criteria:
Has a history of the following conditions:
- Acute promyelocytic leukemia
- Known active central nervous system involvement with AML
- Positive for HIV (HIV testing is not required)
- Positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months
- Cardiovascular disability status of New York Heart Association Class > 2
- Chronic respiratory disease that requires continuous oxygen or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study
- Malabsorption syndrome or other condition that precludes enteral route of administration
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
Sites / Locations
- Arizona Oncology Associates, PC-HOPE /ID# 211509
- Colorado Blood Cancer Institute /ID# 212800
- Rocky Mountain Cancer Centers /ID# 211508
- Fort Wayne Medical Oncology /ID# 223523
- Minnesota Oncology Hematology, PA /ID# 212837
- Oncology Hematology Care, Inc. /ID# 212779
- Willamette Valley Cancer Institute and Research Center /ID# 211504
- Charleston Oncology, P.A. /ID# 211471
- Prisma Health Cancer Inst - Eastside /ID# 211466
- Tennessee Oncology - Chattanooga / McCallie /ID# 212717
- Tennessee Oncology-Nashville Centennial /ID# 210944
- Texas Oncology - Austin Midtown /ID# 212780
- Texas Oncology - Medical City Dallas /ID# 211503
- Texas Transplant Institute /ID# 213311
- Texas Oncology - San Antonio Medical Center /ID# 211510
- Texas Oncology - Northeast Texas /ID# 213908
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Venetoclax 400 mg + azacitidine 75 mg
Venetoclax 400 mg + decitabine 20 mg
Arm Description
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Azacitidine (75 mg/m^2) was administered subcutaneously or intravenously per investigator's choice and institutional practice for 7 days beginning on Day 1 of each 28-day cycle.
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Decitabine (20 mg/m^2) was administered intravenously per investigator's choice and institutional practice for 5 days beginning on Day 1 of each cycle.
Outcomes
Primary Outcome Measures
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
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 bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CR: Absolute neutrophil count (ANC) > 10^3/μL (1,000/μL), platelets > 10^5/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts
CRi: Bone marrow with < 5% blasts, and absolute neutrophils of ≤ 10^3/μL or platelets ≤ 10^5/μL
Secondary Outcome Measures
Percentage of Participants With Complete Remission (CR)
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 bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CR: Absolute neutrophil count (ANC) > 10^3/μL (1,000/μL), platelets > 10^5/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts
Percentage of Participants With Complete Remission With Incomplete Blood Count Recovery (CRi)
The complete remission with incomplete blood count recovery rate is defined as the percentage of participants with complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CRi: Bone marrow with < 5% blasts, and absolute neutrophils of ≤ 10^3/μL or platelets ≤ 10^5/μL.
Percentage of Participants With Post-baseline Transfusion Independence
The transfusion independence rate is defined as the percentage of participants with post-baseline transfusion independence, which is defined as a period of at least 56 days with no transfusion after the first dose of study drug and within 30 days of the last dose of study drug, death, or initiation of post-treatment therapy, whichever is earliest.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03941964
Brief Title
A Study of the Effectiveness of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in Patients With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy
Official Title
A Phase 3b, Single-Arm, Multicenter Open-Label Study of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in AML Patients Ineligible for Intensive Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
August 15, 2019 (Actual)
Primary Completion Date
March 14, 2022 (Actual)
Study Completion Date
March 14, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A study evaluating the effectiveness and safety of venetoclax, in combination with azacitidine or decitabine, in an outpatient setting for treatment-naïve participants with AML who are ineligible for intensive chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Cancer
Keywords
Acute Myeloid Leukemia (AML), Cancer, Treatment-naïve, Venetoclax, Azacitidine, Decitabine, Outpatient setting
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Venetoclax 400 mg + azacitidine 75 mg
Arm Type
Experimental
Arm Description
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Azacitidine (75 mg/m^2) was administered subcutaneously or intravenously per investigator's choice and institutional practice for 7 days beginning on Day 1 of each 28-day cycle.
Arm Title
Venetoclax 400 mg + decitabine 20 mg
Arm Type
Experimental
Arm Description
Participants received venetoclax orally daily for 28-day cycles, for a maximum of 6 cycles, beginning on Cycle 1 Day 1. The venetoclax dosing ramp-up schedule was 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, and 400 mg on Cycle 1 Days 3 -28 and 400 mg daily for each 28-day cycle thereafter. Decitabine (20 mg/m^2) was administered intravenously per investigator's choice and institutional practice for 5 days beginning on Day 1 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, VENCLEXTA, VENCLYXTO
Intervention Description
Venetoclax tablets were to be taken orally once daily with a meal and water in the morning at approximately the same time each day. Tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing. On the days that the participant received either azacitidine or decitabine, venetoclax was dosed in clinic and administered prior to these agents.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
The azacitidine infusion was prepared and administered per the package insert and given either subcutaneously or intravenously, per institutional practice.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
The decitabine infusion was prepared and administered per the package insert and given intravenously, per institutional practice.
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
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 bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CR: Absolute neutrophil count (ANC) > 10^3/μL (1,000/μL), platelets > 10^5/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts
CRi: Bone marrow with < 5% blasts, and absolute neutrophils of ≤ 10^3/μL or platelets ≤ 10^5/μL
Time Frame
Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.
Secondary Outcome Measure Information:
Title
Percentage of Participants With Complete Remission (CR)
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 bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CR: Absolute neutrophil count (ANC) > 10^3/μL (1,000/μL), platelets > 10^5/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts
Time Frame
Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.
Title
Percentage of Participants With Complete Remission With Incomplete Blood Count Recovery (CRi)
Description
The complete remission with incomplete blood count recovery rate is defined as the percentage of participants with complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on bone marrow results and hematology values according to the modified International Working Group (IWG) criteria for AML:
CRi: Bone marrow with < 5% blasts, and absolute neutrophils of ≤ 10^3/μL or platelets ≤ 10^5/μL.
Time Frame
Assessed at Cycle 1 end, at Cycle 2 end if CR/CRi wasn't achieved at Cycle 1 end, or Cycle 4 end if CR/CRi wasn't achieved at Cycle 2 end. Median treatment duration of venetoclax was 16.1 wks (range 3.9-38.1) and 21.1 wks (range 2.7-40.4), respectively.
Title
Percentage of Participants With Post-baseline Transfusion Independence
Description
The transfusion independence rate is defined as the percentage of participants with post-baseline transfusion independence, which is defined as a period of at least 56 days with no transfusion after the first dose of study drug and within 30 days of the last dose of study drug, death, or initiation of post-treatment therapy, whichever is earliest.
Time Frame
From the first dose of study drug to the last dose of study drug +30 days, or death, or initiation of post-treatment therapy, whichever occurred earliest. Median time on follow-up was 183.5 days and 195.0 days, respectively.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant has confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria
Participant is deemed by the investigator to be an appropriate candidate for outpatient ramp-up of venetoclax
Participant is not eligible to receive treatment with standard cytarabine and anthracycline induction regimens
Participant has not received prior treatment for AML (treatment naïve) with the exception of hydroxyurea
Participant has no evidence of spontaneous tumor lysis syndrome (TLS) at Screening
Participant can have progressed from myelodysplastic syndrome (MDS) or be considered to have secondary AML and could have been treated with growth factors or other agents with the exception of hypomethylating agents
Participant has adequate kidney, liver, and hematology laboratory values as detailed in the protocol
Has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 3
Exclusion Criteria:
Has a history of the following conditions:
Acute promyelocytic leukemia
Known active central nervous system involvement with AML
Positive for HIV (HIV testing is not required)
Positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months
Cardiovascular disability status of New York Heart Association Class > 2
Chronic respiratory disease that requires continuous oxygen or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study
Malabsorption syndrome or other condition that precludes enteral route of administration
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, PC-HOPE /ID# 211509
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284-1812
Country
United States
Facility Name
Colorado Blood Cancer Institute /ID# 212800
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rocky Mountain Cancer Centers /ID# 211508
City
Lone Tree
State/Province
Colorado
ZIP/Postal Code
80124
Country
United States
Facility Name
Fort Wayne Medical Oncology /ID# 223523
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
Minnesota Oncology Hematology, PA /ID# 212837
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Oncology Hematology Care, Inc. /ID# 212779
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236-2725
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center /ID# 211504
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401-6043
Country
United States
Facility Name
Charleston Oncology, P.A. /ID# 211471
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414-7710
Country
United States
Facility Name
Prisma Health Cancer Inst - Eastside /ID# 211466
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Tennessee Oncology - Chattanooga / McCallie /ID# 212717
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404-3230
Country
United States
Facility Name
Tennessee Oncology-Nashville Centennial /ID# 210944
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203-1632
Country
United States
Facility Name
Texas Oncology - Austin Midtown /ID# 212780
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Oncology - Medical City Dallas /ID# 211503
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Texas Transplant Institute /ID# 213311
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Texas Oncology - San Antonio Medical Center /ID# 211510
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240-5251
Country
United States
Facility Name
Texas Oncology - Northeast Texas /ID# 213908
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
IPD Sharing Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
IPD Sharing Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
IPD Sharing URL
https://vivli.org/ourmember/abbvie/
Links:
URL
http://www.rxabbvie.com
Description
Related Info
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A Study of the Effectiveness of Venetoclax in Combination With Azacitidine or Decitabine in an Outpatient Setting in Patients With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy
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