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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Azacitidine; Drug: Magrolimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Woden, Australian Capital Territory, Australia, 2606
      • Canberra Hospital
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Border Medical Oncology Research Unit
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Sydney, New South Wales, Australia, 2217
      • St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Monash University, Eastern Health-Box Hill Hospital
    • Epping, Victoria, Australia, 3076
      • Northern Health
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Austria
  • Linz, Austria
    • Ordensklinikum Linz GmbH Elisabethinen
  • Vienna, Austria, 1140
    • Hanusch Krankenhaus
  • Wien, Austria, 1130
    • Wiener Gesundheitsverbund, Klinik Hietzing
• Belgium
  • Antwerp, Belgium, 2060
    • Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium, 9000
    • University Hospital Gent
  • Haine-Saint-Paul, Belgium, 7100
    • Hopital de Jolimont
  • Leuven, Belgium, 3000
    • University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege
• Canada
  • Halifax, Canada, B3H 1V7
    • Queen Elizabeth II (QEII) Health Sciences Centre
  • Montreal, Canada, H1T 2M4
    • Centre Integre Universitaire de Sante et de Services Sociaux(CIUSSS) de l'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre - University Health Network
  • Winnipeg, Canada, R3E 0V9
    • CancerCare Manitoba
• Czechia
  • Jihormoravsky KRAJ, Czechia, 625 00
    • Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika FN Brno a LF MU
  • Olomouc, Czechia, 77520
    • Fakultni nemocine Olomouc, Hemato-onkologicka klinika
  • Ostrava, Czechia, 70852
    • Fakultni nemocnice Ostrava, Klinika hematoonkologie
  • Prague, Czechia, 100 34
    • Fakulti nemocnice Kralovske Vinohrady, Internf hematologicka klinika FNKV a 3. LF UK
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance
• France
  • Amiens Cedex 1, France, 80054
    • CHU Amiens Picardie
  • Angers, France, 49033
    • CHU d'Angers
  • Bobigny, France, 93000
    • Hopital Avicenne
  • Creteil, France, 94010
    • Hôpitaux Universitaires Henri Mondor
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire Grenoble Alpes
  • Le Chesnay Cedex, France, 78157
    • Centre Hospitalier De Versailles
  • Lille Cedex, France, 59037
    • Hôpital Claude Huriez (CHRU de Lillle)
  • Lyon Cedex 08, France, 69373
    • Centre Leon Berard
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire Nantes - Hotel Dieu
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon-Sud (CHLS)
  • Strasbourg, France, 67033
    • Institut de cancérologie Strasbourg Europe (ICANS)
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole
  • Vandoeuvre-les-Nancy, France, 54500
    • CHU de Nancy - Hôpitaux de Brabois
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Braunschweig, Germany, 38114
    • Städtisches Klinikum Braunschweig GmbH Medizinische Klinik III/Hämatologie und Onkologie
  • Dusseldorf, Germany, 40225
    • Universitatsklinikum Dusseldorf, Klink fur Hamatologie, Onkologie und Klinische Immunologie
  • Düsseldorf, Germany, 40479
    • Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatologie und Palliativmedizin
  • Flensburg, Germany, 24939
    • Malteser Krankenhaus St. Franziskus Hospital,Med.Klinik I
  • Frankfurt, Germany, 60590
    • Universitatsklinikum Frankfurt Goethe Universitat Med. Klink II
  • Hamburg, Germany, 20099
    • Asklepios Klink St.Georg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Hamatologie, Hamostaseologie, Onkologie und Stammzelltrandsplantation
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg
  • Minden, Germany, 32429
    • Johannes Wesling Klinikum Minden Universitätsklinik fur Hämatologie, Onkologie, Hämostaseologie und Pastativrndezin, Universitatsklinik der Ruhr-Unive
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar Technischen Universitat Munchen
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg, Rahel-Straus-Straße 10
  • Regensburg, Germany, 93053
    • Universitatsklinikum Regensburg, Klink fur Innere Medizin III
  • Ulm, Germany, 89070
    • Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Klinik fur Innere Medizin III
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
  • Gyor, Hungary, 9024
    • Petz Aladár Egyetemi Oktató Kórház II. Belgyógyaszat - Haematológia
  • Hajdu-bihar, Hungary, 4032
    • Debreceni Egyetem Klinikai Központ Belgyogyaszati Klinika B epulet Hematologia
  • Szeged, Hungary, 6725
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Kozpont
• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital Ein Kerem
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center
• Italy
  • Ancona, Italy, I-60126
    • Azienda Ospedaliero Universitaria delle Marche - SOD Clinica di Ematologia
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
  • Milano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
  • Monza, Italy, 20052
    • ASST Monza-Ospedale San Gerardo
  • Perugia, Italy
    • Azienda Ospedaliera di Perugia - Santa Maria della Misericordia
  • Pesaro, Italy, 61122
    • Azienda Sanitaria Territoriale Pesaro e Urbino - "Stabilimento Ospedaliero San Salvatore - Muraglia" - U.O. Ematologia e Centro Trapianti
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 6591
    • The Catholic University of Korea Seoul Saint Mary's Hospital
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223GZ
    • Jeroen Bosch Ziekenhuis
  • Amersfoort, Netherlands, 3813 TZ
    • Meander Medisch Centrum
  • Amsterdam, Netherlands, 1081 HV
    • Amsterdam Universitair Medische Centra-Locatie Vrije Universiteit Medisch Centrum
  • Breda, Netherlands, 4818 CK
    • Amphia Hospital, department Oncologie, Route 43
  • Den Haag, Netherlands, 2545AA
    • Hagaziekenhuis
  • Enschede, Netherlands, 7512 KZ
    • Medisch Spectrum Twente - Enschede Koningsplein
  • Groningen, Netherlands, 9700 RB
    • Universitair Medisch Centrum Groningen
  • Leeuwarden, Netherlands, 8934 AD
    • Medisch Centrum Leeuwarden
  • Maastricht, Netherlands, 62002
    • Masstricht Universitair Medisch Centrum
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis, Nieuwegein
  • Nijmegen, Netherlands, 6532 SZ
    • Canisius Wilhelmina Ziekenhuis
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus Medisch Centrum
• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital, Department of Hematology
• Poland
  • Lublin, Poland, 20090
    • Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli, Oddzial Hematologiczny
  • Opole, Poland, 45-372
    • Szpital Wojewodozki w Opolu Sp. z 0.0. Oddzial Klinixzny Hematologii, Onkologii Hematologicznej i Chorob Wemnetrznych
  • Łódź, Poland, 93-510
    • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M.Kopernika w Lodzi, Oddzial Hematologii Ogolnej
• Spain
  • Alava, Spain
    • Hospital Universitario Araba
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain
    • Hospital Universitario Quironsalud Madrid
  • Madrid, Spain, 28041
    • Hospital Universitario La Paz
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca - Hospital Clínico
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago de Compostela
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
• Switzerland
  • Berne, Switzerland, 3010
    • Inselspital Universitatsspital Bern
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11490
    • National Cheng Kung University Hospital
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Teaching Hospitals NHS Foundation Trust
  • Bristol, United Kingdom, BS2 8ED
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust
  • Liverpool, United Kingdom, L7 8YA
    • Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Newcastle upon Tyne Hospitals Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
  • Warwick, United Kingdom, CV34 5BW
    • South Warwickshire University NHS Foundation Trust
  • Wolverhampton, United Kingdom, WV10 0QP
    • The Royal Wolverhampton NHS Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Fresno, California, United States, 93730
      • Community Cancer Institute
    • Orange, California, United States, 92868
      • UC Irvine Health- Chao Family Comprehensive Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Research Center
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation - Clinic
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospitals and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Worcester
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • MidAmerica Division, Inc., c/o Research Medical Center
    • Saint Louis, Missouri, United States, 63110
      • SSM Health Saint Louis University Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital
    • New York, New York, United States, 10021
      • New York-Presbyterian/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals, The University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute Hematology- Charlotte
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest Baptist Health
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Cancer Institute Hematology - Forsyth
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain Health - LDS Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Franciscan Health
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Venetoclax; Tablets administered orally; Other Names: VENCLEXTA®; Drug: Azacitidine; Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV); Drug: Magrolimab; Administered intravenously (IV); Other Names: GS-4721
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was measured from the date of randomization to the date of death from any cause. Participants were censored at last known alive date. Kaplan-Meier (KM) estimates were used in outcome measure analysis.	Up to 1.6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)	The CR + CRh rate was defined as the percentage of participants who achieved a CR (including CR without minimal residual disease (CRMRD-) and CR with positive or unknown MRD (CRMRD+/unk)) or CRh as defined by CR with partial platelet and absolute neutrophil count recovery within 6 cycles of treatment while on study prior to initiation of any new anti-acute myeloid leukemia (AML) therapy or stem cell transplant (SCT). CRMRD- and CRMRD+/unk: neutrophils >1.0 ×10^9/L, platelets >100 ×10^9/L, <5% bone marrow blasts, no circulating blasts or extramedullary disease (confirmed by flow cytometry <0.1% sensitivity for CRMRD-) within the response assessment window of 1.6 years. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis. Each cycle was of 28 days.	Up to 1.6 years
Rate of Complete Remission (CR)	CR was defined as the percentage of the participants who achieved CR (including CRMRD- and CRMRD+/unk) within 6 cycles of treatment as determined by the investigator while on study prior to initiation of any new anti-acute myeloid leukemia (AML) therapy or stem cell transplant (SCT) within the response assessment window of 1.6 years. Definitions for CRMRD- and CRMRD+/unk were mentioned in outcome measure #2. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis. Each cycle was of 28 days.	Up to 1.6 years
Event-Free Survival (EFS)	EFS was defined as time from the date of randomization to the earliest date of the documented relapse from CR, treatment failure (defined as failure to achieve CR within 6 cycles of treatment), or death from any cause within the response window. KM estimates were used in outcome measure analysis. CR is defined in outcome measure 2.	Up to 1.6 years
Duration of CR + CRh in Participants Who Achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)	The duration of CR + CRh was measured from the time the assessment criteria were first met for CR (including CRMRD- and CRMRD+/unk) or CRh within 6 cycles of treatment until the first date of AML relapse or death (including assessments post SCT). Those who were not observed to have relapsed disease or death while on study were censored at the date of their last response assessment with no evidence of relapse on or prior to the data cut off date within the response assessment window of 1.6 years. Participants started taking new anti-AML therapies (excluding post-SCT maintenance therapy) before relapse, duration of CR + CRh were censored at the last response assessment before the initiation of the new anti-AML therapies. CR and CRh are defined in Outcome Measure #2. Each cycle was of 28 days.	Up to 1.6 years
Duration of Complete Remission (DCR) in Participants Who Achieved Complete Remission (CR)	The DCR was measured from the time the assessment criteria were first met for CR (including CRMRD- and CRMRD+/unk) within 6 cycles of treatment until the first date of AML relapse or death (including assessments post SCT). Those who were not observed to have relapsed disease or death while on study were censored at the date of their last response assessment with no evidence of relapse on or prior to the data cutoff date within the response assessment window of 1.6 years. Participants started taking new anti-AML therapies (excluding post-SCT maintenance therapy) before relapse, DCR were censored at the last response assessment before the initiation of the new anti-AML therapies. KM estimates were used in outcome measure analysis. CRMRD- and CRMRD+/unk are defined in outcome measure #2. Each cycle was of 28 days.	Up to 1.6 years
Rate of CR/CRh Without Minimal Residual Disease (CR/CRhMRD-)	The CR/CRhMRD- rate was the percentage of participants who achieved a CRMRD- or CRhMRD- within 6 cycles of treatment while on study prior to initiation of any new anti-AML therapy or SCT within the response assessment window of 1.6 years. Each cycle was of 28 days. KM estimates were used for outcome measure analysis. CRhMRD- : neutrophils > 0.5 x 10^9/L; platelets > 50 x 10^9/L; bone marrow blasts < 5%; MRD negative (determined using multiparameter flow cytometry with a sensitivity of < 0.1%). Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. Percentages were rounded off.	Up to 1.6 years
Rate of CR Without Minimal Residual Disease (CRMRD-)	The CRMRD- rate was the percentage of participants who achieved a CRMRD- within 6 cycles of treatment SCT within the response assessment window of 1.6 years. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis. CRMRD is defined in outcome measure #2. Each cycle was of 28 days. Percentages were rounded off	Up to 1.6 years
Red Blood Cell (RBC) Transfusion Independence Conversion Rate	The RBC transfusion independence conversion rate was the percentage of participants who had a 56-day or longer period with no RBC or whole blood transfusions at any time between the date of the first dose of study treatment and discontinuation of study treatment among all participants who were RBC transfusion dependent at baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.	Up to 1.6 years
Platelet Transfusion Independence Conversion Rate	The platelet transfusion independence conversion rate was the percentage of participants who had a 56-day or longer period with no platelet transfusions at any time between the date of the first dose of study treatment and discontinuation of study treatment among all participants who were platelet transfusion dependent at baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.	Up to 1.6 years
Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale	The TTD on the EORTC QLQ-C30 GHS/QoL scale was defined as time from the date of randomization to the time a participant experienced at least 1 threshold value deterioration from baseline or death, whichever was earlier. Questionnaire includes 30 questions resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 1 GHS/QoL scale, 3 symptom scales (fatigue, nausea and vomiting, pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). After linear transformation, all scales and single item measures range in score from 0-100. Higher score on GHS/QoL scale meant better GHS/QoL. KM estimates were used in outcome measure analysis.	Up to 1.6 years
Time to First Deterioration (TTD) on the EORTC QLQ-C30 Physical Functioning Scale	The TTD on the EORTC QLQ-C30 physical functioning scale was defined as time from the date of randomization to the time a participant experienced at least 1 threshold value deterioration from baseline or death, whichever is earlier. Physical functioning scale is one of the five functional scales of the EORTC QLQ C30 questionnaire. After linear transformation, scale range in score from 0-100. A higher score on functional scales means better functioning and better quality of life. KM estimates were used in outcome measure analysis.	Up to 1.6 years
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dose date or the day before initiation of new anti-AML therapy including stem cell transplantation, whichever is earlier. Percentages were rounded-off.	First dose date up to 1.4 years plus 70 days
Percentage of Participants Experiencing Grade 3 or Higher Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 70 days or the day before the initiation of new anti-AML therapy including SCT, whichever came first, and were summarized by treatment group. Severity grades were defined by the CTCAE Version 5.0. 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Life-Threatening; 5 = Death. Percentages were rounded-off.	First dose date up to 1.4 years, plus 70 days
Serum Concentration of Magrolimab Over Time		Predose on Day 1, Day 8, Day 15, Day 29; Predose on Day 57 and 1 hour post-dose; Predose on Day 113, Day 169, Day 253, and Day 337.
Percentage of Participants With Anti-Magrolimab Antibodies	Percentages were rounded off.	Up to 1.6 years
Maximum Levels of Serum Anti-Magrolimab Antibodies		Up to 1.6 years

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): April 11, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Magrolimab; Venetoclax; Azacitidine
• Other Study ID Numbers: GS-US-590-6154; 2021-003434-36 (EudraCT Number); MOH_2022-08-15_011983 (Registry Identifier: Israel Clinical Research Site)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No