Acute Myeloid Leukemia (AML)Phase 3NCT03941964
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 3 study testing Venetoclax, Azacitidine and Decitabine in people with Acute Myeloid Leukemia (AML) and Cancer, run by AbbVie at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Cancer
- What is being tested?
- Venetoclax, Azacitidine and Decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 16 sitesUnited States
- Study dates
- 15 Aug 2019to 14 Mar 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Texas Oncology - Austin Midtown /ID# 212780
Austin, Texas, 78705
Charleston Oncology, P.A. /ID# 211471
Charleston, South Carolina, 29414-7710
Tennessee Oncology - Chattanooga / McCallie /ID# 212717
Chattanooga, Tennessee, 37404-3230
Oncology Hematology Care, Inc. /ID# 212779
Cincinnati, Ohio, 45236-2725
Texas Oncology - Medical City Dallas /ID# 211503
Dallas, Texas, 75230
Colorado Blood Cancer Institute /ID# 212800
Denver, Colorado, 80218
Willamette Valley Cancer Institute and Research Center /ID# 211504
Eugene, Oregon, 97401-6043
Fort Wayne Medical Oncology /ID# 223523
Fort Wayne, Indiana, 46804
Prisma Health Cancer Inst - Eastside /ID# 211466
Greenville, South Carolina, 29615
Rocky Mountain Cancer Centers /ID# 211508
Lone Tree, Colorado, 80124
Minnesota Oncology Hematology, PA /ID# 212837
Minneapolis, Minnesota, 55404
Tennessee Oncology-Nashville Centennial /ID# 210944
Nashville, Tennessee, 37203-1632
Texas Transplant Institute /ID# 213311
San Antonio, Texas, 78229
Texas Oncology - San Antonio Medical Center /ID# 211510
San Antonio, Texas, 78240-5251
Arizona Oncology Associates, PC-HOPE /ID# 211509
Tempe, Arizona, 85284-1812
Texas Oncology - Northeast Texas /ID# 213908
Tyler, Texas, 75702
About this study
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
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.
- Conditions
- Acute Myeloid Leukemia (AML), Cancer
- Being tested
- Venetoclax, Azacitidine, Decitabine
- Keywords
- Acute Myeloid Leukemia (AML), Cancer, Treatment-naïve, Venetoclax, Azacitidine, Decitabine, Outpatient setting
- Medical subject headings
- Leukemia, Myeloid, Acute, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called ABT-199, VENCLEXTA, VENCLYXTO
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.
AzacitidineDrug
Also called Vidaza
The azacitidine infusion was prepared and administered per the package insert and given either subcutaneously or intravenously, per institutional practice.
DecitabineDrug
Also called Dacogen
The decitabine infusion was prepared and administered per the package insert and given intravenously, per institutional practice.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Venetoclax; Drug: 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. Receives: Drug: Venetoclax; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
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
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2019
- Study start15 Aug 2019
- Primary completion14 Mar 2022
- Study completion14 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03941964
- Sponsor's protocol ID
- M19-072
- Status last verified
- Feb 2023
- First submitted
- 3 May 2019
- Last updated
- 20 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
- Expanded access
- Available
Publications
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.
PubMed 38711253