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

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT03941964

Collaborator

(none)

Enrollment

Locations

Arm

30.9

Actual Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML) Cancer	Drug: venetoclax Drug: azacytidine Drug: decitabine	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 15, 2019

Actual Primary Completion Date :

Mar 14, 2022

Actual Study Completion Date :

Mar 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ventoclax + azacitidine or decitabine Venetoclax (daily for 28 days), in combination with azacitidine or decitabine, beginning on Cycle 1 Day 1. Depending on investigator's choice, participants will receive either azacitidine for 7 days beginning on Day 1 of each 28-day cycle or decitabine for 5 days beginning on Day 1 of each 28-day cycle, as per institutional practice.	Drug: venetoclax tablet; oral Other Names: ABT-199 Drug: azacytidine infusion; subcutaneous or intravenous Other Names: Vidaza Drug: decitabine infusion; intravenous Other Names: Dacogen

Arm

Intervention/Treatment

Experimental: Ventoclax + azacitidine or decitabine

Venetoclax (daily for 28 days), in combination with azacitidine or decitabine, beginning on Cycle 1 Day 1. Depending on investigator's choice, participants will receive either azacitidine for 7 days beginning on Day 1 of each 28-day cycle or decitabine for 5 days beginning on Day 1 of each 28-day cycle, as per institutional practice.

Drug: venetoclax

tablet; oral

Other Names:

ABT-199

Drug: azacytidine

infusion; subcutaneous or intravenous

Other Names:

Vidaza

Drug: decitabine

infusion; intravenous

Other Names:

Dacogen

Outcome Measures

Primary Outcome Measures

Composite Complete Remission Rate (CR + CRi) [Up to approximately 24 weeks]
The Composite Complete Remission Rate (CR + CRi) is defined as the proportion of participants who achieve complete remission (CR) plus participants who achieve complete remission with incomplete hematologic recovery (CRi) as described by the modified International Working Group (IWG) criteria for Acute Myeloid Leukemia (AML).

Secondary Outcome Measures

Overall Response Rates (CR, CRi) [Up to approximately 24 weeks]
Overall Response Rates to treatment is the proportion of participants who achieve complete remission or complete remission with incomplete hematologic recovery, based on guidelines adapted from the IWG for AML.
Percent of Participants who Achieve Transfusion Independence [Up to at least 56 days after initial administration of study drug]
Transfusion Independence: the rate of red blood cell (RBC) and platelet transfusion dependence (defined as having received ≥ 2 units of RBCs and/or platelets within 56 days prior to study) at baseline and assess transfusion independence, defined as at least 56 consecutive days without a RBC or platelet transfusion during the treatment period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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