AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 3ENHANCE-2NCT04778397

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

A Phase 3 study testing Magrolimab, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia, run by Gilead Sciences at 156 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Magrolimab, Venetoclax and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
258 participants
Where
156 sitesin 15 countries
Study dates
1 Jul 2021to 25 Mar 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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 red blood cell (RBC)-direct therapies, were 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.

Trial locations and contacts

156 sites in 15 countries.

156 sites in 15 countries

United States36 sites

  • Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Hospitals, The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Northwestern Memorial Hospital/Main Lab

    Chicago, Illinois, 60611

  • The University of Chicago Medical Centre

    Chicago, Illinois, 60637

  • The Ohio State University Wexner Medical Center/ James Cancer Hospital

    Columbus, Ohio, 43210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

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

    Duarte, California, 91010

  • Duke Blood Cancer Center

    Durham, North Carolina, 27705

  • University of Kansas Hospital

    Fairway, Kansas, 66205

  • St. Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute

    Greenville, South Carolina, 29615

  • Baylor College of Medicine Medical Center

    Houston, Texas, 77030

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

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

    Kansas City, Missouri, 64132

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536

  • USC/ Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California, 90095

  • Miami Cancer Institute

    Miami, Florida, 33176

  • Froedtert Hospital / Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Tulane Medical center

    New Orleans, Louisiana, 70112

  • Columbia University Medical Center - Herbert Irving Pavilion

    New York, New York, 10032

  • University of Oklahoma Health Sciences Center - OU Health Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health

    Orange, California, 92868

  • AdventHealth Orlando

    Orlando, Florida, 32804

  • Memorial Cancer Institute

    Pembroke Pines, Florida, 33028

  • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Cancer Center Outpatient Pharmacy

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute ,The University of Utah

    Salt Lake City, Utah, 84112

  • SSM Health Saint Louis University Hospital

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Japan23 sites

  • Hyogo Prefectural Amagasaki General Medical Center

    Amagasaki, 660-8550

  • Chiba Aoba Municipal Hospital

    Chiba, 260-0852

  • University of Yamanashi Hospital

    Chūō, 409-3898

  • Kyushu University Hospital

    Fukuoka, 812-8582

  • Fukushima Medical University Hospital

    Fukushima, 960-1295

  • Aiiku Hospital

    Hokkaido, 064-0804

  • Tokai University School of Medicine

    Isehara, 259-1193

  • Kanazawa University Hospital

    Kanazawa, 920-8641

  • National Cancer Center Hospital East

    Kashiwa, 277-8577

  • Hospital of the University of Occupational and Environmental Health, Japan

    Kitakyushu-shi, 807-8555

  • Kobe City Medical Center General Hospital

    Kobe, 650-0047

  • Gunmaken Saiseikai Maebashi Hospital

    Maebashi, 371-0821

  • Ehime Prefectural Center Hospital

    Matsuyama, 790-0024

  • Nagasaki University Hospital

    Nagasaki, 852-8501

  • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

    Nagoya, 453-8511

  • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

    Nagoya, 466-8650

  • Okayama University Hospital

    Okayama, 700-8558

  • Osaka Metropolitan University Hospital

    Osaka, 545-8586

  • Kindai University Hospital

    Sayama, 589-8511

  • National University Corporation Tohoku University Tohoku University Hospital

    Sendai, 980-8574

  • NTT Medical Center Tokyo

    Shinagawa-Ku, 141-8625

  • Yamagata University Hospital

    Yamagata, 990-9585

  • University of Fukui Hospital

    Yoshida-gun, 910-1193

Other trials in Japan

Spain19 sites

  • Hospital General Universitario de Alicante

    Alicante, 3010

  • Hospital del la Santa Creu i Sant Pau

    Barcelona, 08025

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Institut Catala d'Oncologia

    Barcelona, 08907

  • Complejo Asistencial Universitario de Burgos/H.U. de Burgos

    Burgos, 09006

  • Complejo Hospitalario San Pedro de Alcantara

    Cáceres, 10001

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital Universitario de Gran Canaria Doctor Negrin

    Las Palmas de Gran Canaria, 35010

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Universitario Central de Asturias

    Oviedo, 33011

  • Clinica Universidad de Navarra - Pamplona (Main Site)

    Pamplona, 31008

  • Complejo Asistencial Universitario de Salamanca - Hsopital Clinico

    Salamanca, 37007

  • Hospital U. Marques de Valdecilla

    Santander, 39008

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital Universitari I Politècnic La Fe

    Valencia, 46026

Other trials in Spain

Germany13 sites

  • Uniklinik RWTH Aachen, Medizinische Klunuk IV - Klinik fur Hamatologie, Onkologie, Hamastaseologie und Srammzelltransplantation

    Aachen, 52074

  • Dept. of Hematology, Oncology and Tumor Immunology, Charite- University Medicine Berlin, Campus Virchow Klinikum

    Berlin, 13353

  • Department of Hematology and Oncology, Braunschweig Community Hospital

    Braunschweig, 38114

  • Universitatsklinikum Koln

    Cologne, 50937

  • Universitatsklinikum Carl Gustav Carus Dresden an der Technische Universitat Dresden, Medizinische Klinik und Poliklinik 1, Bereich Hamatologie

    Dresden, 01307

  • Universitätsklinikum Düsseldorf -Klinik für Hämatologie, Onkologie und Klinische Immunologie

    Düsseldorf, 40225

  • Dept. of Medicine II, University Hospital Hamburg-Eppendorf

    Hamburg, 20246

  • Universitatsklinikum Heidelberg, Innere Medizin V, Hamatologie, Onkologie und Rheumatologie

    Heidelberg, 69120

  • Universitatsklinikum Schleswig-Holstein

    Kiel, 24105

  • Klinikum Ludwigshafen Medizinische Klinik A

    Ludwigshafen, 67063

  • LMU - Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik III, Campus Grosshadern

    München, 81377

  • Klinikum rechts der Isar der Technischen Universitat Munchen, Klinik und Poliklinik fur Innere Medizin III

    München, 81675

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

    Ulm, 89081

Other trials in Germany

France12 sites

  • CHU d'Angers

    Angers, 49933

  • CHU de Caen

    Caen, 14033

  • CHRU Lille - Hospital Claude Huriez

    Lille, 59037

  • CHU Limoges

    Limoges, 87042

  • Central Hospital Lyon Sud

    Lyon, 69495

  • Institut Paoli Calmettes

    Marseille, 13009

  • CHU de Nantes, Hotel Dieu

    Nantes, 44093

  • CHU Nice - Hopital Archet 1

    Nice, 6200

  • Gustave Roussy

    Paris, 94805

  • Hopital Haut-Leveque

    Pessac, 33604

  • IUCT Oncopole

    Toulouse, 31059

  • Hopitaux de Brabois

    Vandœuvre-lès-Nancy

Other trials in France

United Kingdom12 sites

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2GW

  • United Lincolnshire Hospitals NHS Trust, Pilgrim Hospital, Sibsey Road

    Boston, PE21 9QS

  • Cambridge University Hospital NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Cardiff and Vale University Health Board

    Cardiff Wales, CF14 4XW

  • Barts Health NHS Trust

    City of London, EC1A 7BE

  • NHS Tayside

    Dundee, DD1 9SY

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2PG

  • King's College NHS Foundation Trust

    London, SE5 9RS

  • Oxford University Hospital NHS Foundation Trust

    Oxford, OX3 7LE

  • The Royal Marsden NHS Foundation Trust

    Sutton, SM2 5PT

  • The Christie NHS Foundation Trust

    Withington, M20 4BX

Other trials in United Kingdom

Australia10 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Canberra Hospital

    Garran, Australian Capital Territory, 2605

  • Andrew Love Cancer Centre, University Hospital Geelong

    Geelong, Victoria, 3220

  • The Alfred

    Melbourne, Victoria, 3004

  • St Vincents Hospital Melbourne

    Melbourne, Victoria, 3122

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Calvary Master Newcastle

    Waratah, New South Wales, 2298

  • Westmead Hospital / Department of Haematology and Bone Marrow Transplantation

    Westmead, New South Wales, 2145

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Italy10 sites

  • Azienda Ospedaliero Universitaria delle Marche

    Ancona, I-60126

  • AOU Consorziale Policlinico Bari

    Bari, 70124

  • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola-Malphigi U.O Ematologia

    Bologna, 40138

  • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRS - Oncologia Medica

    Meldola, 40174

  • Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli U.O.S.C. di Ematologia con Trapianto di Midollo Osseo

    Naples, 80131

  • SC Ematologia, Azienda Ospedaliera di Perugia - Santa Maria della Misericordia

    Perugia, 06129

  • AORM - AO Riuniti Marche Norde - Pesaro Presidio "San Salvatore" - Muraglia

    Pesaro, 61122

  • Fondazione PTV Policinico Tor Vergata

    Roma, 00133

  • SCDU Ematologia e Terrapie cellulari AO O Ordine Mauriziano Torino

    Torino, 10122

  • ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi

    Varese, 21100

Other trials in Italy

Belgium6 sites

  • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV

    Bruges, 8000

  • Universitair Ziekenhuis Brussel

    Brussels

  • Grand Hôpital De Charleroi - Notre Dame

    Charleroi, 6000

  • Universitaire Ziekenhuis Antwerpen

    Edegem

  • Universitair Ziekenhuis Gent

    Ghent, 9000

  • AZ Delta vzw

    Roeselare, 8800

Other trials in Belgium

Canada6 sites

  • Tom Baker Cancer Center

    Calgary, T2N 4N2

  • Queen Elizabeth II Health Sciences Centre

    Halifax, B3H 1V7

  • CIUSSS de L'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont

    Montreal, H1T 2M4

  • McGill University Health Centre

    Montreal, H4A 3J1

  • Sunnybrook Research Institute

    Toronto, M4N 3M5

  • Princess Margaret Cancer Centre

    Toronto, M5G 2M9

Other trials in Canada

Austria2 sites

  • Univ. -Klinik für Hämatologie und Internistische Onkologie, Kepler Universitätskilkun GmbHMed

    Linz, 4021

  • Uniklinikum Salzburg, Universitatsklinik f. Innere Medizin III der PMU

    Salzburg, 5020

Other trials in Austria

Denmark2 sites

  • Aalborg University Hospital

    Aalborg, 9000

  • Odense University Hospital

    Odense C, 5000

Other trials in Denmark

Hong Kong2 sites

  • Prince of Wales Hospital, The Chinese University of Hong Kong

    Hong Kong

  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

Switzerland2 sites

  • Universitatsspital Basel - Klinik fur Hamatrologie, Bereich Innere Medizin

    Basel, 4031

  • Inselspital, Universitatsspital Bern - Universitatsklinik fur Medizinisch Onkologie

    Bern, CH 3010

Other trials in Switzerland

Sweden1 site

  • Universitetssjukhus, Hematologimottagnungen

    Lund, 221 85

Other trials in Sweden

About this study

Official title: 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).

Being tested
Magrolimab, Venetoclax, Azacitidine, Cytarabine, Daunorubicin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MagrolimabDrug

    Also called GS-4721

    Administered intravenously (IV).

  • VenetoclaxDrug

    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).

  • AzacitidineDrug

    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).

  • CytarabineDrug

    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.

  • DaunorubicinDrug

    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).

  • IdarubicinDrug

    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).

  • Steroidal Eye DropsDrug

    Administered per institutional standard during consolidation.

Study groups in NCT04778397
Study groupRoleWhat they receive
Magrolimab + AzacitidineExperimentalParticipants will receive an escalating dose of magrolimab and a fixed dose of azacitidine.
Receives: Drug: Magrolimab; Drug: Azacitidine
Control Arm: Venetoclax + AzacitidineActive comparatorParticipants who are appropriate for non-intensive therapy will receive an escalating dose of venetoclax and a fixed dose of azacitidine.
Receives: Drug: Venetoclax; Drug: Azacitidine
Control Arm: 7+3 ChemotherapyActive comparatorParticipants 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.
Receives: Drug: Cytarabine; Drug: Daunorubicin; Drug: Idarubicin; Drug: Steroidal Eye Drops

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS) in Participants Appropriate for Non-intensive Therapy

    OS was measured from the date of randomization to the date of death from any cause. Deaths which were not observed during the study were censored at their last known alive date.

    Kaplan-Meier (KM) estimates were used in outcome measure analysis.

    Measured: Up to 2.1 years

Secondary outcomes (11)

  1. Overall Survival in All Participants

    OS was measured from the date of randomization to the date of death from any cause. Deaths which were not observed during the study were censored at their last known alive date.

    KM estimates were used in outcome measure analysis.

    Measured: Up to 2.1 years

  2. Event-Free Survival (EFS) in All Participants

    EFS: time from randomization to earliest relapse from CR (CR without minimal residual disease (CRMRD-) and CR with MRD positive/MRD unknown (CRMRD+/unk)), treatment failure (failure to achieve CR in 6 months of magrolimab/venetoclax+azacitidine; 2 months after chemotherapy), or death within the response window. 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-). Post-SCT assessments or new AML therapies were included. Date of randomization was assigned as event date for participants with treatment failure. Participants without events were censored at their last assessment. KM estimates were used for analysis.

    Measured: Up to 2.1 years

  3. Rate of Complete Remission (CR) in All Participants

    The rate of CR was the percentage of participants who achieved 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) within the response assessment window of 2.1 years. CR MRD- and CR MRD+/unk are defined in Outcome Measure#3 (EFS). Percentages were rounded-off.

    Clopper-Pearson method were used in outcome measure analysis.

    Measured: Up to 2.1 years

  4. Rate of CR Without Minimal Residual Disease (CR MRD-) in All Participants

    Rate of CR MRD- was 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 within the response assessment window of 2.1 years. CR MRD- is defined in Outcome Measure #3 (EFS). Percentages were rounded-off.

    Clopper-Pearson method were used in outcome measure analysis.

    Measured: Up to 2.1 years

  5. Rate of CR and CR With Partial Hematologic Recovery (CR+CRh) in All Participants

    The CR+CRh rate was the percentage of participants who achieved a CR (including CR MRD- and CR MRD+/unk) or CRh as defined by CR with partial platelet and absolute neutrophil count (ANC) recovery within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy while on study prior to initiation of any new anti-AML therapy or SCT up to the response assessment window of 2.1 years. CRh is defined as neutrophils > 0.5 x 10^9/L; platelets > 50 x 10^9/L; bone marrow blasts < 5%; Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CR MRD- and CR MRD+/unk are defined in Outcome Measure#3 (EFS). Percentages were rounded-off.

    Clopper-Pearson method were used in outcome measure analysis.

    Measured: Up to 2.1 years

  6. Duration of CR (DCR)

    DCR was measured from the time the assessment criteria were 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). Participants 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. Participants who started taking new anti-AML therapies (excluding post-SCT maintenance therapy) before relapse, the DCR were censored at the last response assessment before the initiation of the new anti-AML therapies. CR MRD- and CR MRD+/unk are defined in Outcome Measure#3 (EFS).

    KM estimates were used in outcome measure analysis.

    Measured: Up to 2.1 years

  7. Duration of CR+CRh

    Duration of CR+CRh was measured from the time the assessment criteria were 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). Participants 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. Participants who started taking new anti-AML therapies (excluding post-SCT maintenance therapy) before relapse, the duration of CR + CRh were censored at the last response assessment before the initiation of the new anti-AML therapies. CR MRD- and CR MRD+/un are defined in Outcome Measure #3. CRh is defined in Outcome Measure #6.

    KM estimates were used for outcome measure analysis.

    Measured: Up to 2.1 years

  8. Percentage of Participants Experiencing Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)

    TEAEs were defined as any AE that began on or after the date of first dose of study treatment up to the date of last dose of study treatment plus 70 days or the day before initiation of new anti-AML therapy including SCT, whichever occurred first. Percentages were rounded-off.

    Measured: First dose date up to 1.3 years plus 70 days

  9. Percentage of Participants Experiencing Grade 3 or 4 Treatment-Emergent Laboratory Abnormalities

    Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study treatment plus 70 days or the day before initiation of any new anti-AML therapy including SCT, whichever occurred first. Percentages were rounded-off.

    Measured: First dose date up to 1.3 years plus 70 days

  10. Serum Concentration of Magrolimab

    Measured: Predose on Days 1, 4, 8, 11; Days 29 and 57 Predose and 1 hour Postdose; Predose on Days 113, 169, 253, 281 and 337

  11. Percentage of Participants With Anti-Magrolimab Antibodies

    Percentages were rounded-off.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2021
  2. Study start1 Jul 2021
  3. Primary completion25 Mar 2024
  4. Study completion25 Mar 2024

Why it stopped: Study discontinued due to futility.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
258 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04778397
Sponsor's protocol ID
GS-US-546-5857
Other IDs
2020-003949-11, jRCT2071220076
Acronym
ENHANCE-2
Status last verified
Feb 2025
First submitted
23 Feb 2021
Last updated
5 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Zeidner JF, Sallman DA, Recher C, Daver NG, Leung AYH, Hiwase DK, Subklewe M, Pabst T, Montesinos P, Larson RA, Wilde L, Enjeti AK, Kawashima I, Papayannidis C, O'Nions J, Johnson L, Dong M, Huang J, Bagheri T, Hacohen Kleiman G, Lee C, Vyas P. Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study. Blood. 2025 Jul 31;146(5):590-600. doi: 10.1182/blood.2024027408.

    PubMed 40009500

  • 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.

    PubMed 37703506

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Magrolimab, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia, run by Gilead Sciences at 156 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 156 sites in United States, Japan, Spain, Germany, France and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) in Participants Appropriate for Non-intensive Therapy (time frame: Up to 2.1 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04778397, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2025.

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