Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia

NCT ID: NCT05079230

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 378 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-07
• Study Completion Date: 2024-04-11

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Magrolimab

Intervention Type: DRUG

Administered intravenously (IV)

Venetoclax

Intervention Type: DRUG

Tablets administered orally

Azacitidine

Intervention Type: DRUG

Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)

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.

Group Type: PLACEBO_COMPARATOR

Venetoclax

Intervention Type: DRUG

Tablets administered orally

Azacitidine

Intervention Type: DRUG

Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)

Placebo

Intervention Type: DRUG

Administered intravenously (IV)

Interventions

Magrolimab

Administered intravenously (IV)

Intervention Type: DRUG

Venetoclax

Tablets administered orally

Intervention Type: DRUG

Azacitidine

Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)

Intervention Type: DRUG

Placebo

Administered intravenously (IV)

Intervention Type: DRUG

Other Intervention Names

GS-4721; VENCLEXTA®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States

Community Cancer Institute

Fresno, California, United States

UC Irvine Health- Chao Family Comprehensive Cancer Center

Orange, California, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Loyola University Medical Center

Maywood, Illinois, United States

Parkview Research Center

Fort Wayne, Indiana, United States

Indiana Blood and Marrow Transplantation - Clinic

Indianapolis, Indiana, United States

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

University of Massachusetts Worcester

Worcester, Massachusetts, United States

MidAmerica Division, Inc., c/o Research Medical Center

Kansas City, Missouri, United States

SSM Health Saint Louis University Hospital

St Louis, Missouri, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

New York-Presbyterian/Weill Cornell Medical Center

New York, New York, United States

Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Novant Health Cancer Institute Hematology- Charlotte

Charlotte, North Carolina, United States

Novant Health Cancer Institute Hematology - Forsyth

Winston-Salem, North Carolina, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Baylor University Medical Center

Dallas, Texas, United States

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Houston Methodist Hospital Cancer Center

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Intermountain Health - LDS Hospital

Salt Lake City, Utah, United States

Virginia Mason Franciscan Health

Seattle, Washington, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Canberra Hospital

Woden, Australian Capital Territory, Australia

Border Medical Oncology Research Unit

Albury, New South Wales, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services

Sydney, New South Wales, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Monash University, Eastern Health-Box Hill Hospital

Box Hill, Victoria, Australia

Northern Health

Epping, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Ordensklinikum Linz GmbH Elisabethinen

Linz, , Austria

Wiener Gesundheitsverbund, Klinik Hietzing

Vienna, , Austria

Hanusch Krankenhaus

Vienna, , Austria

Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

University Hospital Gent

Ghent, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Universitaire de Liege

Liège, , Belgium

Queen Elizabeth II (QEII) Health Sciences Centre

Halifax, , Canada

Centre Integre Universitaire de Sante et de Services Sociaux(CIUSSS) de l'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont

Montreal, , Canada

Princess Margaret Cancer Centre - University Health Network

Toronto, , Canada

CancerCare Manitoba

Winnipeg, , Canada

Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika FN Brno a LF MU

Jihormoravsky KRAJ, , Czechia

Fakultni nemocine Olomouc, Hemato-onkologicka klinika

Olomouc, , Czechia

Fakultni nemocnice Ostrava, Klinika hematoonkologie

Ostrava, , Czechia

Fakulti nemocnice Kralovske Vinohrady, Internf hematologicka klinika FNKV a 3. LF UK

Prague, , Czechia

Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance

Prague, , Czechia

CHU Amiens Picardie

Amiens, , France

CHU d'Angers

Angers, , France

Hopital Avicenne

Bobigny, , France

Hopitaux Universitaires Henri Mondor

Créteil, , France

Centre Hospitalier Universitaire Grenoble Alpes

La Tronche, , France

Centre Hospitalier de Versailles

Le Chesnay, , France

Hôpital Claude Huriez (CHRU de Lillle)

Lille, , France

Centre Leon Berard

Lyon, , France

Centre Hospitalier Universitaire Nantes - Hotel Dieu

Nantes, , France

Hopital Saint-Louis

Paris, , France

Centre Hospitalier Lyon-Sud (CHLS)

Pierre-Bénite, , France

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, , France

Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole

Toulouse, , France

CHU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, , France

Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Städtisches Klinikum Braunschweig GmbH Medizinische Klinik III/Hämatologie und Onkologie

Braunschweig, , Germany

Universitatsklinikum Dusseldorf, Klink fur Hamatologie, Onkologie und Klinische Immunologie

Düsseldorf, , Germany

Marien Hospital Dusseldorf GmbH, Klinik Fur Onkologie, Hamatologie Und Palliativmedizin

Düsseldorf, , Germany

Malteser Krankenhaus St. Franziskus Hospital,Med.Klinik I

Flensburg, , Germany

Universitatsklinikum Frankfurt Goethe Universitat Med. Klink II

Frankfurt, , Germany

Asklepios Klink St.Georg

Hamburg, , Germany

Medizinische Hochschule Hannover, Hamatologie, Hamostaseologie, Onkologie und Stammzelltrandsplantation

Hanover, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Johannes Wesling Klinikum Minden Universitätsklinik fur Hämatologie, Onkologie, Hämostaseologie und Pastativrndezin, Universitatsklinik der Ruhr-Unive

Minden, , Germany

Klinikum rechts der Isar Technischen Universitat Munchen

München, , Germany

Klinikum Oldenburg, Rahel-Straus-Straße 10

Oldenburg, , Germany

Universitatsklinikum Regensburg, Klink fur Innere Medizin III

Regensburg, , Germany

Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Klinik fur Innere Medizin III

Ulm, , Germany

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, , Hong Kong

Princess Margaret Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Tuen Mun Hospital

Hong Kong, , Hong Kong

Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika

Budapest, , Hungary

Petz Aladár Egyetemi Oktató Kórház II. Belgyógyaszat - Haematológia

Győr, , Hungary

Debreceni Egyetem Klinikai Központ Belgyogyaszati Klinika B epulet Hematologia

Hajdu-bihar, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Kozpont

Szeged, , Hungary

Rambam Health Care Campus

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Azienda Ospedaliero Universitaria delle Marche - SOD Clinica di Ematologia

Ancona, , Italy

ASST Papa Giovanni XXIII

Bergamo, , Italy

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

IRCCS Istituto Clinico Humanitas

Milan, , Italy

ASST Monza-Ospedale San Gerardo

Monza, , Italy

Azienda Ospedaliera di Perugia - Santa Maria della Misericordia

Perugia, , Italy

Azienda Sanitaria Territoriale Pesaro e Urbino - "Stabilimento Ospedaliero San Salvatore - Muraglia" - U.O. Ematologia e Centro Trapianti

Pesaro, , Italy

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Amsterdam Universitair Medische Centra-Locatie Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Amphia Hospital, department Oncologie, Route 43

Breda, , Netherlands

Medisch Spectrum Twente - Enschede Koningsplein

Enschede, , Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Masstricht Universitair Medisch Centrum

Maastricht, , Netherlands

St. Antonius Ziekenhuis, Nieuwegein

Nieuwegein, , Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

HagaZiekenhuis

The Hague, , Netherlands

Oslo University Hospital, Department of Hematology

Oslo, , Norway

Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M.Kopernika w Lodzi, Oddzial Hematologii Ogolnej

Lodz, , Poland

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli, Oddzial Hematologiczny

Lublin, , Poland

Szpital Wojewodozki w Opolu Sp. z 0.0. Oddzial Klinixzny Hematologii, Onkologii Hematologicznej i Chorob Wemnetrznych

Opole, , Poland

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

The Catholic University of Korea Seoul Saint Mary's Hospital

Seoul, , South Korea

Hospital Universitario Araba

Alava, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Quironsalud Madrid

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Complejo Asistencial Universitario de Salamanca - Hospital Clinico

Salamanca, , Spain

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Universitari I Politecnic La Fe

Valencia, , Spain

Inselspital Universitätsspital Bern

Bern, , Switzerland

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

National Cheng Kung University Hospital

Taipei, , Taiwan

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, , United Kingdom

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, , United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

King's College Hospital

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Newcastle upon Tyne Hospitals Foundation Trust

Newcastle upon Tyne, , United Kingdom

Oxford University Hospitals NHS Foundation Trust, Churchill Hospital

Oxford, , United Kingdom

South Warwickshire University NHS Foundation Trust

Warwick, , United Kingdom

The Royal Wolverhampton NHS Trust

Wolverhampton, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Czechia; France; Germany; Hong Kong; Hungary; Israel; Italy; Netherlands; Norway; Poland; South Korea; Spain; Switzerland; Taiwan; United Kingdom

References

Daver N, Vyas P, Huls G, Dohner H, Maury S, Novak J, Papayannidis C, Martinez Chamorro C, Montesinos P, Niroula R, Fenaux P, Esteve J, Wu SJ, De Voeght A, Mayer J, Valk PJM, Johnson L, Dong M, Liu K, Kuwahara S, Caldwell K, Guru Murthy GS. The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy. Blood. 2025 Jul 31;146(5):601-611. doi: 10.1182/blood.2024027506.

Reference Type: DERIVED

PMID: 40233321 (View on PubMed)

Daver NG, Vyas P, Kambhampati S, Al Malki MM, Larson RA, Asch AS, Mannis G, Chai-Ho W, Tanaka TN, Bradley TJ, Jeyakumar D, Wang ES, Sweet K, Kantarjian HM, Garcia-Manero G, Komrokji R, Xing G, Ramsingh G, Renard C, Zeidner JF, Sallman DA. Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results. J Clin Oncol. 2023 Nov 1;41(31):4893-4904. doi: 10.1200/JCO.22.02604. Epub 2023 Sep 13.

Reference Type: DERIVED

PMID: 37703506 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=GS-US-590-6154

Gilead Clinical Trials Website

Other Identifiers

2021-003434-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOH_2022-08-15_011983

Identifier Type: REGISTRY

Identifier Source: secondary_id

GS-US-590-6154

Identifier Type: -

Identifier Source: org_study_id