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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03941964
• Other study ID #: M19-072
• Status: Completed
• Phase: Phase 3
• Start date: August 15, 2019
• Est. completion date: March 14, 2022

Study information

• Verified date: February 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 14, 2022
• Est. primary completion date: March 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Cancer
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.

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