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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine; Drug: Decitabine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284-1812
      • Arizona Oncology Associates, PC-HOPE /ID# 211509
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute /ID# 212800
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers /ID# 211508
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology /ID# 223523
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, PA /ID# 212837
  • Ohio
    • Cincinnati, Ohio, United States, 45236-2725
      • Oncology Hematology Care, Inc. /ID# 212779
  • Oregon
    • Eugene, Oregon, United States, 97401-6043
      • Willamette Valley Cancer Institute and Research Center /ID# 211504
  • South Carolina
    • Charleston, South Carolina, United States, 29414-7710
      • Charleston Oncology, P.A. /ID# 211471
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Inst - Eastside /ID# 211466
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404-3230
      • Tennessee Oncology - Chattanooga / McCallie /ID# 212717
    • Nashville, Tennessee, United States, 37203-1632
      • Tennessee Oncology-Nashville Centennial /ID# 210944
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin Midtown /ID# 212780
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas /ID# 211503
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute /ID# 213311
    • San Antonio, Texas, United States, 78240-5251
      • Texas Oncology - San Antonio Medical Center /ID# 211510
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas /ID# 213908

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax 400 mg + azacitidine 75 mg; 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.	Drug: Venetoclax; 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.; Other Names: ABT-199; VENCLEXTA; VENCLYXTO; Drug: Azacitidine; The azacitidine infusion was prepared and administered per the package insert and given either subcutaneously or intravenously, per institutional practice.; Other Names: Vidaza
Experimental: Venetoclax 400 mg + decitabine 20 mg; 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.	Drug: Venetoclax; 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.; Other Names: ABT-199; VENCLEXTA; VENCLYXTO; Drug: Decitabine; The decitabine infusion was prepared and administered per the package insert and given intravenously, per institutional practice.; Other Names: Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Measures

Outcome Measure	Measure Description	Time Frame
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	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.
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.	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.
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.	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.

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): March 14, 2022

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Decitabine; Venetoclax; Azacitidine; Acute Myeloid Leukemia (AML); Treatment-naïve; Outpatient setting
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Venetoclax; Azacitidine
• Other Study ID Numbers: M19-072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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