Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated (ENHANCE-2)

A Phase 3, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Patients With TP53 Mutant Acute Myeloid Leukemia

The goal of this clinical study is to compare the effectiveness of the study drugs, magrolimab in combination with azacitidine, versus venetoclax in combination with azacitidine in participants with previously untreated TP53 mutant acute myeloid leukemia (AML).

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Venetoclax; Drug: Cytarabine; Drug: Daunorubicin; Drug: Idarubicin; Drug: Steroidal Eye Drops; Drug: Magrolimab

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Master Newcastle
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital / Department of Haematology and Bone Marrow Transplantation
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Andrew Love Cancer Centre, University Hospital Geelong
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
    • Melbourne, Victoria, Australia, 3122
      • St Vincents Hospital Melbourne
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Austria
  • Linz, Austria, 4021
    • Univ. -Klinik für Hämatologie und Internistische Onkologie, Kepler Universitätskilkun GmbHMed
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg, Universitatsklinik f. Innere Medizin III der PMU
• Belgium
  • Brugge, Belgium, 8000
    • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV
  • Brussels, Belgium
    • Universitair Ziekenhuis Brussel
  • Charleroi, Belgium, 6000
    • Grand Hôpital De Charleroi - Notre Dame
  • Edegem, Belgium
    • Universitaire Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Roeselare, Belgium, 8800
    • AZ Delta vzw
• Canada
  • Calgary, Canada, T2N 4N2
    • Tom Baker Cancer Center
  • Halifax, Canada, B3H 1V7
    • Queen Elizabeth II Health Sciences Centre
  • Montreal, Canada, H4A 3J1
    • McGill University Health Centre
  • Montreal, Canada, H1T 2M4
    • CIUSSS de L'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre
  • Toronto, Canada, M4N 3M5
    • Sunnybrook Research Institute
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Odense C, Denmark, 5000
    • Odense University Hospital
• France
  • Angers cedex, France, 49933
    • CHU d'Angers
  • Caen cedex, France, 14033
    • CHU de Caen
  • Lille, France, 59037
    • CHRU Lille - Hospital Claude Huriez
  • Limoges, France, 87042
    • CHU Limoges
  • Lyon, France, 69495
    • Central Hospital Lyon Sud
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Nantes, France, 44093
    • CHU de Nantes, Hotel Dieu
  • Nice, France, 6200
    • CHU Nice - Hopital Archet 1
  • Paris, France, 94805
    • Gustave Roussy
  • Pessac, France, 33604
    • Hôpital Haut-Lévêque
  • Toulouse, France, 31059
    • IUCT Oncopole
  • Vandoeuvre-lès-Nancy, France
    • Hôpitaux de Brabois
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH Aachen, Medizinische Klunuk IV - Klinik fur Hamatologie, Onkologie, Hamastaseologie und Srammzelltransplantation
  • Berlin, Germany, 13353
    • Dept. of Hematology, Oncology and Tumor Immunology, Charite- University Medicine Berlin, Campus Virchow Klinikum
  • Braunschweig, Germany, 38114
    • Department of Hematology and Oncology, Braunschweig Community Hospital
  • Dresden, Germany, 01307
    • Universitatsklinikum Carl Gustav Carus Dresden an der Technische Universitat Dresden, Medizinische Klinik und Poliklinik 1, Bereich Hamatologie
  • Dusseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf -Klinik für Hämatologie, Onkologie und Klinische Immunologie
  • Hamburg, Germany, 20246
    • Dept. of Medicine II, University Hospital Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg, Innere Medizin V, Hamatologie, Onkologie und Rheumatologie
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • Köln, Germany, 50937
    • Universitatsklinikum Koln
  • Ludwigshafen, Germany, 67063
    • Klinikum Ludwigshafen Medizinische Klinik A
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universitat Munchen, Klinik und Poliklinik fur Innere Medizin III
  • München, Germany, 81377
    • LMU - Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik III, Campus Grosshadern
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Innere Medizin III
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital, The Chinese University of Hong Kong
• Italy
  • Ancona, Italy, I-60126
    • Azienda Ospedaliero Universitaria delle Marche
  • Bari, Italy, 70124
    • AOU Consorziale Policlinico Bari
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola-Malphigi U.O Ematologia
  • Meldola, Italy, 40174
    • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRS - Oncologia Medica
  • Napoli, Italy, 80131
    • Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli U.O.S.C. di Ematologia con Trapianto di Midollo Osseo
  • Perugia, Italy, 06129
    • SC Ematologia, Azienda Ospedaliera di Perugia - Santa Maria della Misericordia
  • Pesaro, Italy, 61122
    • AORM - AO Riuniti Marche Norde - Pesaro Presidio "San Salvatore" - Muraglia
  • Roma, Italy, 00133
    • Fondazione PTV Policinico Tor Vergata
  • Torino, Italy, 10122
    • SCDU Ematologia e Terrapie cellulari AO O Ordine Mauriziano Torino
  • Varese, Italy, 21100
    • ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi
• Japan
  • Amagasaki, Japan, 660-8550
    • Hyogo Prefectural Amagasaki General Medical Center
  • Chiba, Japan, 260-0852
    • Chiba Aoba Municipal Hospital
  • Chuo-City, Japan, 409-3898
    • University of Yamanashi Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukushima-Shi, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Hokkaido, Japan, 064-0804
    • Aiiku Hospital
  • Isehara, Japan, 259-1193
    • Tokai University School of Medicine
  • Kanazawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East
  • Kitakyushu-shi, Japan, 807-8555
    • Hospital of the University of Occupational and Environmental Health, Japan
  • Kobe-city, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Maebashi, Japan, 371-0821
    • Gunmaken Saiseikai Maebashi Hospital
  • Matsuyama, Japan, 790-0024
    • Ehime Prefectural Center Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagoya, Japan, 453-8511
    • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
  • Nagoya-Shi, Japan, 466-8650
    • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Okayama-Shi, Japan, 700-8558
    • Okayama University Hospital
  • Osaka-Shi, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Osakasayama, Japan, 589-8511
    • Kindai University Hospital
  • Sendai, Japan, 980-8574
    • National University Corporation Tohoku University Tohoku University Hospital
  • Shinagawa-Ku, Japan, 141-8625
    • NTT Medical Center Tokyo
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Yoshida-gun, Japan, 910-1193
    • University of Fukui Hospital
• Spain
  • Alicante, Spain, 3010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Institut Catala d'Oncologia
  • Barcelona, Spain, 08025
    • Hospital del la Santa Creu i Sant Pau
  • Burgos, Spain, 09006
    • Complejo Asistencial Universitario de Burgos/H.U. de Burgos
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Cáceres, Spain, 10001
    • Complejo Hospitalario San Pedro de Alcantara
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital Universitario de Gran Canaria Doctor Negrin
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center Madrid
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra - Pamplona (Main Site)
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca - Hsopital Clinico
  • Santander, Spain, 39008
    • Hospital U. Marques de Valdecilla
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
• Sweden
  • Lund, Sweden, 221 85
    • Universitetssjukhus, Hematologimottagnungen
• Switzerland
  • Basel, Switzerland, 4031
    • Universitatsspital Basel - Klinik fur Hamatrologie, Bereich Innere Medizin
  • Berne, Switzerland, CH 3010
    • Inselspital, Universitatsspital Bern - Universitatsklinik fur Medizinisch Onkologie
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS Foundation Trust
  • Boston, United Kingdom, PE21 9QS
    • United Lincolnshire Hospitals NHS Trust, Pilgrim Hospital, Sibsey Road
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospital NHS Foundation Trust
  • Cardiff Wales, United Kingdom, CF14 4XW
    • Cardiff and Vale University Health Board
  • City of London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust
  • Dundee, United Kingdom, DD1 9SY
    • NHS Tayside
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College NHS Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospital NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
  • Withington, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90033
      • USC/ Norris Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • UC Irvine Health
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital/Main Lab
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Centre
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center Outpatient Pharmacy
  • 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 York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Herbert Irving Pavilion
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Hospitals, The University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke Blood Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center/ James Cancer Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center - OU Health Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • St. Francis Cancer Center
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute ,The University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital / 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:

• Individuals with confirmation of acute myeloid leukemia (AML) by World Health Organization criteria, previously untreated for AML, and who have presence of at least 1 TP53 gene mutation that is not benign or likely benign based on evaluation by either central laboratory or an approved local laboratory (after central review of the bone marrow TP53 mitigation next-generation sequencing test results) (individuals with biallelic 17p deletions, loss of both 17p alleles, are eligible based on locally evaluated cytogenetics/karyotype/fluorescence in situ hybridization (FISH) report).
• Individuals with white blood cell (WBC) count ≤ 20×10^3/microliter (μL) prior to randomization. If the individual's WBC is > 20×10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20×10^3/μL prior to the first dose of study treatment and prior to each magrolimab dose the first 4 weeks (if the individual is randomized to the experimental arm) Note: Individuals can be treated with hydroxyurea and/or leukapheresis throughout the study or prior to randomization to reduce the WBC to ≤ 20×10^3/μL to enable eligibility for study drug dosing.
• The hemoglobin must be ≥ 9 grams per deciliter (g/dL) prior to initial dose of study treatment.

Notes: Transfusions are allowed to meet hemoglobin eligibility.

• Individual has provided informed consent.
• Individual is willing and able to comply with clinic visits and procedure outlined in the study protocol.
• Individuals must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, except for individuals less than 75 years of age and appropriate for non-intensive treatment. For these individuals, the ECOG performance status score may be 0 to 3.
• Individuals must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 milliliters per minute calculated by the Cockcroft Gault formula.

• Adequate cardiac function as demonstrated by:

  • Lack of symptomatic congestive heart failure and clinically significant cardiac arrhythmias and ischemic heart disease.
  • Left ventricular ejection fraction (LVEF) > 50% for individuals appropriate for intensive therapy.

• Adequate liver function as demonstrated by:

  • Aspartate aminotransferase ≤ 3.0 × upper limit of normal (ULN).
  • Alanine aminotransferase ≤ 3.0 × ULN.
  • Total bilirubin ≤ 1.5 × ULN, or primary unconjugated bilirubin ≤ 3.0 × ULN if individual has a documented history of Gilbert's syndrome or genetic equivalent.
• Pretreatment blood cross-match completed.
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Individuals must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (aspirate and trephines).

Key Exclusion Criteria:

• Positive serum pregnancy test.
• Breastfeeding female.
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.

• 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 (excluding hydroxyurea), hypomethylating agent (HMA), low dose cytarabine and/or venetoclax.

Note: Individuals with prior myelodysplastic syndrome (MDS) who have not received prior HMAs or chemotherapeutic agents for MDS are allowed on study. Other prior MDS therapies including, but not limited to, lenalidomide, erythroid stimulating agents, or similar RBC-direct therapies, are allowed. Localized non-central nervous system (CNS) radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer, hormonal therapy or maintenance for breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors are also not criteria for exclusion.

• Individuals who are appropriate for intensive treatment but who have been previously treated with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones will be excluded.
• Individuals receiving any live vaccine within 4 weeks prior to initiation of study treatments.
• For individuals appropriate for intensive therapy, individuals treated with trastuzumab within 7 months prior to initiation of study treatments.
• Current participation in another interventional clinical study.
• Known inherited or acquired bleeding disorders.
• Individuals appropriate for non-intensive therapy, who have received treatment with strong and/or moderate cytochrome P450 enzyme 3A (CYP3A) inducers within 7 days prior to the initiation of study treatments.
• Individuals appropriate for non-intensive therapy who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment.
• Individuals appropriate for non-intensive therapy who have malabsorption syndrome or other conditions that preclude enteral route of administration.
• Clinical suspicion of active CNS involvement with AML.
• Individuals who have acute promyelocytic leukemia.
• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
• 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 anti-cancer therapies and have had no evidence of active malignancy for at least ≥ 1 year Note: Individuals on maintenance therapy alone who have no evidence of active malignancy for at least ≥ 1 year are eligible.
• Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or human immunodeficiency virus (HIV) infection in medical history.

• Active HBV, and/or active HCV, and/or HIV following testing at screening:

  • Individuals who test positive for hepatitis B surface antigen (HBsAg). Individuals who test positive for hepatitis B core antibody (anti-HBc) will require HBV deoxyribose nucleic acid (DNA) by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
  • Individuals who test positive for HCV antibody. These individuals will require HCV ribose nucleic acid (RNA) quantitative PCR for confirmation of active disease.
  • Individuals who test positive for HIV antibody.
  • Individuals not currently receiving antiviral therapy and who have an undetectable viral load in the prior 3 months may be eligible for the study.

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: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magrolimab + Azacitidine; Participants will receive an escalating dose of magrolimab and a fixed dose of azacitidine.	Drug: Azacitidine; Administered either subcutaneously (SC) or IV, 75 milligrams per square meter (mg/m^2) on Days 1-7 or Days 1-5, 8 and 9 during every cycle (Cycle=28 days).; Drug: Magrolimab; Administered intravenously (IV).; Other Names: GS-4721
Active Comparator: Control Arm: Venetoclax + Azacitidine; Participants who are appropriate for non-intensive therapy will receive an escalating dose of venetoclax and a fixed dose of azacitidine.	Drug: Azacitidine; Administered either subcutaneously (SC) or IV, 75 milligrams per square meter (mg/m^2) on Days 1-7 or Days 1-5, 8 and 9 during every cycle (Cycle=28 days).; Drug: Venetoclax; Administered orally at a dose of 100 milligrams (mg) on Day 1, 200 mg on Day 2, 400 mg on Days 3-28 during Cycle 1, followed by 400 mg on Days 1-28 during every cycle (Cycle=28 days).
Active Comparator: Control Arm: 7+3 Chemotherapy; Participants who are appropriate for intensive therapy will receive 7+3 chemotherapy: 7 day treatment with cytarabine and 3 day treatment with daunorubicin or idarubicin during induction and high-dose cytarabine and steroidal eye drops during consolidation.	Drug: Cytarabine; Induction: administered continuous infusion, 100 or 200 mg/m^2 on Days 1-7 (7+3 induction) and if needed Days 1-5 (5+2 induction) during a cycle (Cycle=Up to 42 Days). Consolidation: administered IV, 1500 or 3000 mg/m^2 on Days 1, 3, and 5 once every 12 hours for up to 4 cycles.; Drug: Daunorubicin; Administered IV peripherally (IVP), 60 mg/m^2 on Days 1-3 (7+3 induction) and if needed Days 1-2 (5+2 induction) during a cycle (Cycle=Up to 42 days).; Drug: Idarubicin; Administered IV, 12 mg/m^2 on Days 1-3 (7+3 induction) and if needed Days 1-2 (5+2 induction) during a cycle (Cycle=Up to 42 days).; Drug: Steroidal Eye Drops; Administered per institutional standard during consolidation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Participants Appropriate for Non-intensive Therapy	The OS is measured from the date of randomization to the date of death from any cause. Those whose deaths are not observed during the study will be censored at their last known alive date.	Randomization up to death or end of study (up to 27 months) whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival in All Participants	The OS is measured from the date of randomization to the date of death from any cause. Those whose deaths are not observed during the study will be censored at their last known alive date.	Randomization up to death or end of study (up to 27 months) whichever occurs first
Event-Free Survival (EFS) in All Participants	The EFS is defined as time from the date of randomization to the earliest date of documented relapse from complete remission (CR), treatment failure (defined as failure to achieve CR within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or up to 2 months of treatment with 7 + 3 chemotherapy), or death from any cause. Response assessments or death post SCT or new anti-AML therapies will be included. Those who are not observed to have one of these events during the study will be censored at the date of their last response assessment with clear documentation of no relapse during the study. The date of randomization will be assigned as the event date for participants with treatment failure.	Randomization up to end of study (up to 27 months)
Rate of CR and Complete Remission with Partial Hematologic Recovery (CR+CRh) in All Participants	The CR+CRh rate is the percentage of participants who achieve a CR (including CR MRD- and CR MRD+/unk) or CRh as defined by CR with partial platelet and absolute neutrophil count (ANC) recovery while on study prior to initiation of any new anti-AML therapy or SCT.	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Percentage of Participants Experiencing Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0		First dose date up to last dose date (Maximum: 24 months) plus 70 days
Percentage of Participants Experiencing Grade ≥ 3 Treatment-Emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0		First dose date up to last dose date (Maximum: 24 months) plus 70 days
Serum Concentration of Magrolimab		Within 72 hours predose on Day 1 of Cycle 1, within 12 hours predose on Day 8 of Cycle 1 and Day 1 of Cycles 2, 3, 5, 7, 10, 13, and end of treatment (EOT) EOT=Maximum: 24 months (Cycle=28 days)
Rate of Anti-Magrolimab Antibody Incidence	Rate of anti-magrolimab antibody incidence is defined as the percentage of participants with anti-magrolimab antibodies.	Within 72 hours predose on Day 1 of Cycle 1, within 12 hours predose on Day 1 of Cycles 2, 3, 5, 7, 10, 13 and end of treatment (EOT) EOT=Maximum: 24 months (Cycle=28 days)
Rate of Complete Remission (CR) in All Participants	The rate of CR is the percentage of participants who achieve a CR, including CR without minimal residual disease (CR MRD-) and CR with positive or unknown minimal residual disease (CR MRD+/unk) within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, as defined by investigators based on European Leukemia Net (ELN) 2017 AML (ELN 2017 AML) with modifications, while on study prior to initiation of any new anti-AML therapy or stem cell transplant (SCT).	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Rate of CR Without Minimal Residual Disease (CR MRD-) in All Participants	The rate of CR MRD- is the percentage of participants who achieve a CR MRD- within 6 months treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, as defined by investigators based on ELN 2017 AML with modifications, while on study prior to initiation of any new anti-AML therapy or SCT.	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Duration of Complete Remission (DCR)	The DCR is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, until the first date of AML relapse or death (including assessments post SCT). Those who are not observed to have relapsed disease or death while on study will be censored at the date of their last response assessment with no evidence of relapse. If participants start taking new anti-AML therapies (excluding maintenance therapy) before relapse, the DCR will be censored at the last response assessment before the initiation of the new anti-AML therapies.	First CR achieved within 6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy up to the end of study (up to 27 months)
Duration of CR+CRh	The duration of CR+CRh is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) or CRh within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, until the first date of AML relapse or death (including assessments post SCT). Those who are not observed to have relapsed disease or death while on study will be censored at the date of their last response assessment with no evidence of relapse. If patients start taking new anti-AML therapies (excluding maintenance therapy) before relapse, the duration of CR + CRh will be censored at the last response assessment before the initiation of the new anti-AML therapies.	First CR or CRh achieved within 6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy up to the end of study (up to 27 months)

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 1, 2021
• Primary Completion (Actual): March 25, 2024
• Study Completion (Actual): March 25, 2024

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Pharmaceutical Solutions; Venetoclax; Azacitidine; Ophthalmic Solutions; Cytarabine; Daunorubicin; Idarubicin; Magrolimab
• Other Study ID Numbers: GS-US-546-5857; 2020-003949-11 (EudraCT Number); jRCT2071220076 (Other Identifier: Japan Registry of Clinical Trials)

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