Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia (ENHANCE-3)

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Venetoclax; Drug: Magrolimab; Drug: Azacitidine; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05079230

2021-003434-36 (EudraCT Number)

MOH_2022-08-15_011983 (Registry Identifier)

GS-US-590-6154

Details and patient eligibility

About

The goal of this clinical study is to compare the study drugs, magrolimab + venetoclax + azacitidine, versus placebo + venetoclax + azacitidine in participants with untreated acute myeloid leukemia (AML) who are not able to have chemotherapy.

Enrollment: 378 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:

  • ≥ 75 years of age; Or

  • ≥ 18 to 74 years of age with at least 1 of the following comorbidities:

    • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
    • Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
    • Left ventricular ejection fraction ≤ 50%
    • Baseline creatinine clearance ≥ 30 mL/min to < 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
    • Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
    • Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy

  • ECOG performance status:

    • Of 0 to 2 for individuals ≥ 75 years of age Or
    • Of 0 to 3 for individuals ≥ 18 to 74 years of age

• Individuals with white blood cell (WBC) count ≤ 20 x 10^3/μL prior to randomization. If the individual's WBC is > 20 x10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20 x 10^3/μL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle 1.

  • Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to ≤ 20 x 10^3/μL to enable eligibility for study drug dosing

• Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment

  • Note: Transfusions are allowed to meet hemoglobin eligibility

• Pretreatment blood cross-match completed

Key Exclusion Criteria:

• Prior treatment with any of the following:

  • cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα)-targeting agents

  • Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea

    • Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.

• Clinical suspicion of or documented active central nervous system (CNS) involvement with AML

• Individuals who have acute promyelocytic leukemia

• Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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378 participants in 2 patient groups, including a placebo group

Magrolimab + Venetoclax + Azacitidine

Experimental group

Description:

Participants will receive * magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter * venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter * azacitidine: 75 mg/m\^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle Each cycle is 28 days.

Treatment:

Drug: Azacitidine

Drug: Magrolimab

Drug: Venetoclax

Magrolimab Matching Placebo + Venetoclax + Azacitidine

Placebo Comparator group

Description:

Participants will receive * magrolimab matching placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter * venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter * azacitidine: 75 mg/m\^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle Each cycle is 28 days.

Treatment:

Drug: Placebo

Drug: Azacitidine

Drug: Venetoclax