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

AbbVie

Status and phase: Completed; Phase 3

Conditions: Acute Myeloid Leukemia (AML); Cancer

Treatments: Drug: Azacitidine; Drug: Decitabine; Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT03941964

M19-072

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 12+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Venetoclax 400 mg + azacitidine 75 mg

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Azacitidine

Venetoclax 400 mg + decitabine 20 mg

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Decitabine