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

Phase 3

Completed

Conditions: Acute Myeloid Leukemia (AML)
Cancer

Interventions: Drug: Venetoclax
Drug: Azacitidine
Drug: Decitabine

Registration Number: NCT03941964

Lead Sponsor: AbbVie

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Venetoclax 400 mg + azacitidine 75 mg	Azacitidine	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.
Venetoclax 400 mg + decitabine 20 mg	Venetoclax	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.
Venetoclax 400 mg + azacitidine 75 mg	Venetoclax	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.
Venetoclax 400 mg + decitabine 20 mg	Decitabine	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)	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.	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

Name	Time	Method
Percentage of Participants With Complete Remission (CR)	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.	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 Post-baseline Transfusion Independence	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.	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.
Percentage of Participants With Complete Remission With Incomplete Blood Count Recovery (CRi)	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.	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.

Trial Locations

Locations (16): Rocky Mountain Cancer Centers /ID# 211508
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Lone Tree, Colorado, United States
Tennessee Oncology - Chattanooga / McCallie /ID# 212717
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Chattanooga, Tennessee, United States
Prisma Health Cancer Inst - Eastside /ID# 211466
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Greenville, South Carolina, United States
Arizona Oncology Associates, PC-HOPE /ID# 211509
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Tempe, Arizona, United States
Oncology Hematology Care, Inc. /ID# 212779
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Cincinnati, Ohio, United States
Texas Transplant Institute /ID# 213311
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San Antonio, Texas, United States
Texas Oncology - San Antonio Medical Center /ID# 211510
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San Antonio, Texas, United States
Tennessee Oncology-Nashville Centennial /ID# 210944
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Nashville, Tennessee, United States
Colorado Blood Cancer Institute /ID# 212800
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Denver, Colorado, United States
Fort Wayne Medical Oncology /ID# 223523
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Fort Wayne, Indiana, United States
Minnesota Oncology Hematology, PA /ID# 212837
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Minneapolis, Minnesota, United States
Willamette Valley Cancer Institute and Research Center /ID# 211504
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Eugene, Oregon, United States
Texas Oncology - Medical City Dallas /ID# 211503
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Dallas, Texas, United States
Charleston Oncology, P.A. /ID# 211471
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Charleston, South Carolina, United States
Texas Oncology - Northeast Texas /ID# 213908
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Tyler, Texas, United States
Texas Oncology - Austin Midtown /ID# 212780
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Austin, Texas, United States