NCT03941964

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Aug 2019

Typical duration for phase_3

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 3, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 8, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

August 15, 2019

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 14, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 14, 2022

Completed
1 year until next milestone

Results Posted

Study results publicly available

March 20, 2023

Completed
Last Updated

March 20, 2023

Status Verified

February 1, 2023

Enrollment Period

2.6 years

First QC Date

May 3, 2019

Results QC Date

February 22, 2023

Last Update Submit

February 22, 2023

Conditions

Keywords

Acute Myeloid Leukemia (AML)CancerTreatment-naïveVenetoclaxAzacitidineDecitabineOutpatient setting

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • 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.

  • 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.

  • 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.

Study Arms (2)

Venetoclax 400 mg + azacitidine 75 mg

EXPERIMENTAL

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: VenetoclaxDrug: Azacitidine

Venetoclax 400 mg + decitabine 20 mg

EXPERIMENTAL

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: VenetoclaxDrug: Decitabine

Interventions

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.

Also known as: ABT-199, VENCLEXTA, VENCLYXTO
Venetoclax 400 mg + azacitidine 75 mgVenetoclax 400 mg + decitabine 20 mg

The azacitidine infusion was prepared and administered per the package insert and given either subcutaneously or intravenously, per institutional practice.

Also known as: Vidaza
Venetoclax 400 mg + azacitidine 75 mg

The decitabine infusion was prepared and administered per the package insert and given intravenously, per institutional practice.

Also known as: Dacogen
Venetoclax 400 mg + decitabine 20 mg

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Arizona Oncology Associates, PC-HOPE /ID# 211509

Tempe, Arizona, 85284-1812, United States

Location

Colorado Blood Cancer Institute /ID# 212800

Denver, Colorado, 80218, United States

Location

Rocky Mountain Cancer Centers /ID# 211508

Lone Tree, Colorado, 80124, United States

Location

Fort Wayne Medical Oncology /ID# 223523

Fort Wayne, Indiana, 46804, United States

Location

Minnesota Oncology Hematology, PA /ID# 212837

Minneapolis, Minnesota, 55404, United States

Location

Oncology Hematology Care, Inc. /ID# 212779

Cincinnati, Ohio, 45236-2725, United States

Location

Willamette Valley Cancer Institute and Research Center /ID# 211504

Eugene, Oregon, 97401-6043, United States

Location

Charleston Oncology, P.A. /ID# 211471

Charleston, South Carolina, 29414-7710, United States

Location

Prisma Health Cancer Inst - Eastside /ID# 211466

Greenville, South Carolina, 29615, United States

Location

Tennessee Oncology - Chattanooga / McCallie /ID# 212717

Chattanooga, Tennessee, 37404-3230, United States

Location

Tennessee Oncology-Nashville Centennial /ID# 210944

Nashville, Tennessee, 37203-1632, United States

Location

Texas Oncology - Austin Midtown /ID# 212780

Austin, Texas, 78705, United States

Location

Texas Oncology - Medical City Dallas /ID# 211503

Dallas, Texas, 75230, United States

Location

Texas Transplant Institute /ID# 213311

San Antonio, Texas, 78229, United States

Location

Texas Oncology - San Antonio Medical Center /ID# 211510

San Antonio, Texas, 78240-5251, United States

Location

Texas Oncology - Northeast Texas /ID# 213908

Tyler, Texas, 75702, United States

Location

Related Publications (1)

  • Manda S, Anz BM 3rd, Benton C, Broun ER, Yimer HA, Renshaw JS, Geils G Jr, Berdeja J, Cruz J, Melear JM, Fanning S, Fletcher L, Li Y, Duan Y, Werner ME, Potluri J, Pai MV, Donnellan WB. A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia. Hematol Oncol. 2024 May;42(3):e3274. doi: 10.1002/hon.3274.

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteNeoplasms

Interventions

venetoclaxAzacitidineDecitabine

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Results Point of Contact

Title
Global Medical Services
Organization
AbbVie

Study Officials

  • ABBVIE INC.

    AbbVie

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

May 3, 2019

First Posted

May 8, 2019

Study Start

August 15, 2019

Primary Completion

March 14, 2022

Study Completion

March 14, 2022

Last Updated

March 20, 2023

Results First Posted

March 20, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
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/
More information

Locations