Study Stopped
Study was terminated due to futility
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
3 other identifiers
interventional
378
19 countries
161
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2022
161 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 4, 2021
CompletedFirst Posted
Study publicly available on registry
October 15, 2021
CompletedStudy Start
First participant enrolled
July 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 11, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
April 11, 2024
CompletedResults Posted
Study results publicly available
April 4, 2025
CompletedApril 4, 2025
April 1, 2025
1.8 years
October 4, 2021
February 25, 2025
April 3, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (16)
Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)
Up to 1.6 years
Rate of Complete Remission (CR)
Up to 1.6 years
Event-Free Survival (EFS)
Up to 1.6 years
Duration of CR + CRh in Participants Who Achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)
Up to 1.6 years
Duration of Complete Remission (DCR) in Participants Who Achieved Complete Remission (CR)
Up to 1.6 years
- +11 more secondary outcomes
Study Arms (2)
Magrolimab + Venetoclax + Azacitidine
EXPERIMENTALParticipants 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.
Magrolimab Matching Placebo + Venetoclax + Azacitidine
PLACEBO COMPARATORParticipants 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.
Interventions
Administered intravenously (IV)
Tablets administered orally
Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)
Eligibility Criteria
You may qualify if:
- 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
- +2 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (164)
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010, United States
Community Cancer Institute
Fresno, California, 93730, United States
UC Irvine Health- Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Baptist MD Anderson Cancer Center
Jacksonville, Florida, 32207, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
Indiana Blood and Marrow Transplantation - Clinic
Indianapolis, Indiana, 46237, United States
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201, United States
University of Massachusetts Worcester
Worcester, Massachusetts, 01655, United States
MidAmerica Division, Inc., c/o Research Medical Center
Kansas City, Missouri, 64132, United States
SSM Health Saint Louis University Hospital
St Louis, Missouri, 63110, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
New York-Presbyterian/Weill Cornell Medical Center
New York, New York, 10021, United States
Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital
New York, New York, 10029, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Novant Health Cancer Institute Hematology- Charlotte
Charlotte, North Carolina, 28204, United States
Novant Health Cancer Institute Hematology - Forsyth
Winston-Salem, North Carolina, 27103, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27103, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
West Penn Hospital
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234, United States
Houston Methodist Hospital Cancer Center
Houston, Texas, 77030, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Intermountain Health - LDS Hospital
Salt Lake City, Utah, 84143, United States
Virginia Mason Franciscan Health
Seattle, Washington, 98101, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Canberra Hospital
Woden, Australian Capital Territory, 2606, Australia
Border Medical Oncology Research Unit
Albury, New South Wales, 2640, Australia
Concord Repatriation General Hospital
Concord, New South Wales, 2139, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services
Sydney, New South Wales, 2217, Australia
Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Monash University, Eastern Health-Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Northern Health
Epping, Victoria, 3076, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Ordensklinikum Linz GmbH Elisabethinen
Linz, Austria
Wiener Gesundheitsverbund, Klinik Hietzing
Vienna, 1130, Austria
Hanusch Krankenhaus
Vienna, 1140, Austria
Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg
Antwerp, 2060, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
University Hospital Gent
Ghent, 9000, Belgium
Hopital de Jolimont
Haine-Saint-Paul, 7100, Belgium
University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liege
Liège, 4000, Belgium
Queen Elizabeth II (QEII) Health Sciences Centre
Halifax, B3H 1V7, Canada
Centre Integre Universitaire de Sante et de Services Sociaux(CIUSSS) de l'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont
Montreal, H1T 2M4, Canada
Princess Margaret Cancer Centre - University Health Network
Toronto, M5G 2M9, Canada
CancerCare Manitoba
Winnipeg, R3E 0V9, Canada
Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika FN Brno a LF MU
Jihormoravsky KRAJ, 625 00, Czechia
Fakultni nemocine Olomouc, Hemato-onkologicka klinika
Olomouc, 77520, Czechia
Fakultni nemocnice Ostrava, Klinika hematoonkologie
Ostrava, 70852, Czechia
Fakulti nemocnice Kralovske Vinohrady, Internf hematologicka klinika FNKV a 3. LF UK
Prague, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance
Prague, 128 08, Czechia
CHU Amiens Picardie
Amiens, 80054, France
CHU d'Angers
Angers, 49033, France
Hopital Avicenne
Bobigny, 93000, France
Hopitaux Universitaires Henri Mondor
Créteil, 94010, France
Centre Hospitalier Universitaire Grenoble Alpes
La Tronche, 38700, France
Centre Hospitalier de Versailles
Le Chesnay, 78157, France
Hôpital Claude Huriez (CHRU de Lillle)
Lille, 59037, France
Centre Leon Berard
Lyon, 69373, France
Centre Hospitalier Universitaire Nantes - Hotel Dieu
Nantes, 44093, France
Hopital Saint-Louis
Paris, 75010, France
Centre Hospitalier Lyon-Sud (CHLS)
Pierre-Bénite, 69495, France
Institut de Cancérologie Strasbourg Europe (ICANS)
Strasbourg, 67033, France
Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole
Toulouse, 31059, France
CHU de Nancy - Hopitaux de Brabois
Vandœuvre-lès-Nancy, 54500, France
Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie
Berlin, 13353, Germany
Universitätsklinikum Bonn
Bonn, 53127, Germany
Städtisches Klinikum Braunschweig GmbH Medizinische Klinik III/Hämatologie und Onkologie
Braunschweig, 38114, Germany
Universitatsklinikum Dusseldorf, Klink fur Hamatologie, Onkologie und Klinische Immunologie
Düsseldorf, 40225, Germany
Marien Hospital Dusseldorf GmbH, Klinik Fur Onkologie, Hamatologie Und Palliativmedizin
Düsseldorf, 40479, Germany
Malteser Krankenhaus St. Franziskus Hospital,Med.Klinik I
Flensburg, 24939, Germany
Universitatsklinikum Frankfurt Goethe Universitat Med. Klink II
Frankfurt, 60590, Germany
Asklepios Klink St.Georg
Hamburg, 20099, Germany
Medizinische Hochschule Hannover, Hamatologie, Hamostaseologie, Onkologie und Stammzelltrandsplantation
Hanover, 30625, Germany
Universitätsklinikum Magdeburg
Magdeburg, 39120, Germany
Johannes Wesling Klinikum Minden Universitätsklinik fur Hämatologie, Onkologie, Hämostaseologie und Pastativrndezin, Universitatsklinik der Ruhr-Unive
Minden, 32429, Germany
Klinikum rechts der Isar Technischen Universitat Munchen
München, 81675, Germany
Klinikum Oldenburg, Rahel-Straus-Straße 10
Oldenburg, 26133, Germany
Universitatsklinikum Regensburg, Klink fur Innere Medizin III
Regensburg, 93053, Germany
Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Klinik fur Innere Medizin III
Ulm, 89070, 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, 1083, Hungary
Petz Aladár Egyetemi Oktató Kórház II. Belgyógyaszat - Haematológia
Győr, 9024, Hungary
Debreceni Egyetem Klinikai Központ Belgyogyaszati Klinika B epulet Hematologia
Hajdu-bihar, 4032, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Kozpont
Szeged, 6725, Hungary
Rambam Health Care Campus
Haifa, 31096, Israel
Shaare Zedek Medical Center
Jerusalem, 9103102, Israel
Hadassah University Hospital Ein Kerem
Jerusalem, 91120, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
The Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Azienda Ospedaliero Universitaria delle Marche - SOD Clinica di Ematologia
Ancona, I-60126, Italy
ASST Papa Giovanni XXIII
Bergamo, 24127, Italy
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
Bologna, 40138, Italy
IRCCS Istituto Clinico Humanitas
Milan, 20089, Italy
ASST Monza-Ospedale San Gerardo
Monza, 20052, 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, 61122, Italy
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223GZ, Netherlands
Meander Medisch Centrum
Amersfoort, 3813 TZ, Netherlands
Amsterdam Universitair Medische Centra-Locatie Vrije Universiteit Medisch Centrum
Amsterdam, 1081 HV, Netherlands
Amphia Hospital, department Oncologie, Route 43
Breda, 4818 CK, Netherlands
Medisch Spectrum Twente - Enschede Koningsplein
Enschede, 7512 KZ, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9700 RB, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, 8934 AD, Netherlands
Masstricht Universitair Medisch Centrum
Maastricht, 62002, Netherlands
St. Antonius Ziekenhuis, Nieuwegein
Nieuwegein, 3435 CM, Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, 6532 SZ, Netherlands
Erasmus Medisch Centrum
Rotterdam, 3000 CA, Netherlands
HagaZiekenhuis
The Hague, 2545AA, Netherlands
Oslo University Hospital, Department of Hematology
Oslo, 0424, Norway
Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M.Kopernika w Lodzi, Oddzial Hematologii Ogolnej
Lodz, 93-510, Poland
Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli, Oddzial Hematologiczny
Lublin, 20090, Poland
Szpital Wojewodozki w Opolu Sp. z 0.0. Oddzial Klinixzny Hematologii, Onkologii Hematologicznej i Chorob Wemnetrznych
Opole, 45-372, Poland
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Severance Hospital
Seoul, 120-752, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
The Catholic University of Korea Seoul Saint Mary's Hospital
Seoul, 6591, South Korea
Hospital Universitario Araba
Alava, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28009, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz
Madrid, 28041, Spain
Hospital Universitario Quironsalud Madrid
Madrid, Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Complejo Asistencial Universitario de Salamanca - Hospital Clinico
Salamanca, 37007, Spain
Complejo Hospitalario Universitario de Santiago de Compostela
Santiago de Compostela, 15706, Spain
Hospital Universitari I Politecnic La Fe
Valencia, 46026, Spain
Inselspital Universitätsspital Bern
Bern, 3010, Switzerland
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
China Medical University Hospital
Taichung, 404, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
National Cheng Kung University Hospital
Taipei, 11490, Taiwan
Blackpool Teaching Hospitals NHS Foundation Trust
Blackpool, FY3 8NR, United Kingdom
University Hospitals Bristol and Weston NHS Foundation Trust
Bristol, BS2 8ED, United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF, United Kingdom
Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA, United Kingdom
Barts Health NHS Trust
London, EC1A 7BE, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Newcastle upon Tyne Hospitals Foundation Trust
Newcastle upon Tyne, NE7 7DN, United Kingdom
Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
Oxford, OX3 7LE, United Kingdom
South Warwickshire University NHS Foundation Trust
Warwick, CV34 5BW, United Kingdom
The Royal Wolverhampton NHS Trust
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (2)
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.
PMID: 40233321DERIVEDDaver 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.
PMID: 37703506DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
October 4, 2021
First Posted
October 15, 2021
Study Start
July 7, 2022
Primary Completion
April 11, 2024
Study Completion
April 11, 2024
Last Updated
April 4, 2025
Results First Posted
April 4, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will not share