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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Magrolimab + Venetoclax + Azacitidine 		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.
  • Drug: Magrolimab
    Administered intravenously (IV)
    Other names:
    • GS-4721
  • Drug: Venetoclax
    Tablets administered orally
    Other names:
    • VENCLEXTA®
  • Drug: Azacitidine
    Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)
Placebo Comparator
Magrolimab Matching Placebo + Venetoclax + Azacitidine 		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.
  • Drug: Venetoclax
    Tablets administered orally
    Other names:
    • VENCLEXTA®
  • Drug: Azacitidine
    Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)
  • Drug: Placebo
    Administered intravenously (IV)

Recruiting Locations

More Details

NCT ID
NCT05079230
Status
Terminated
Sponsor
Gilead Sciences

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.