Study Details

OVERVIEW

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 (ENHANCE-3)

PROTOCOL 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.

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Acute Myeloid Leukemia

Gender

N/A

Date

July 2022 - April 2024

Study Type

INTERVENTIONAL

Study Phase

PHASE3

Product

Magrolimab, Venetoclax, Azacitidine, Placebo

Eligibility Information

Inclusion Criteria

Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:
≥ 75 years of age; Or
≥ 18 to 74 years of age with at least 1 of the following comorbidities:
Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
Left ventricular ejection fraction ≤ 50%
Baseline creatinine clearance ≥ 30 mL/min to < 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
ECOG performance status:
Of 0 to 2 for individuals ≥ 75 years of age Or
Of 0 to 3 for individuals ≥ 18 to 74 years of age
Individuals with white blood cell (WBC) count ≤ 20 x 10^3/μL prior to randomization. If the individual's WBC is > 20 x10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20 x 10^3/μL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle 1.
Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to ≤ 20 x 10^3/μL to enable eligibility for study drug dosing
Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment
Note: Transfusions are allowed to meet hemoglobin eligibility
Pretreatment blood cross-match completed

Exclusion Criteria

Prior treatment with any of the following:
cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα)-targeting agents
Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea
Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.
Clinical suspicion of or documented active central nervous system (CNS) involvement with AML
Individuals who have acute promyelocytic leukemia
Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations

Locations (164)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

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

Duarte, California, United States, 91010

Community Cancer Institute

Fresno, California, United States, 93730

UC Irvine Health- Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States, 32207

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Loyola University Medical Center

Maywood, Illinois, United States, 60153

Parkview Research Center

Fort Wayne, Indiana, United States, 46845

Indiana Blood and Marrow Transplantation - Clinic

Indianapolis, Indiana, United States, 46237

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

University of Massachusetts Worcester

Worcester, Massachusetts, United States, 01655

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

Kansas City, Missouri, United States, 64132

SSM Health Saint Louis University Hospital

Saint Louis, Missouri, United States, 63110

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08901

New York-Presbyterian/Weill Cornell Medical Center

New York, New York, United States, 10021

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

New York, New York, United States, 10029

University of Rochester Medical Center

Rochester, New York, United States, 14642

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27514

Novant Health Cancer Institute Hematology- Charlotte

Charlotte, North Carolina, United States, 28204

Novant Health Cancer Institute Hematology - Forsyth

Winston-Salem, North Carolina, United States, 27103

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27103

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States, 97213

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

West Penn Hospital

Pittsburgh, Pennsylvania, United States, 15224

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

Baylor University Medical Center

Dallas, Texas, United States, 75246

Brooke Army Medical Center

Fort Sam Houston, Texas, United States, 78234

Houston Methodist Hospital Cancer Center

Houston, Texas, United States, 77030

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Intermountain Health - LDS Hospital

Salt Lake City, Utah, United States, 84143

Virginia Mason Franciscan Health

Seattle, Washington, United States, 98101

Fred Hutchinson Cancer Center

Seattle, Washington, United States, 98109

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Canberra Hospital

Woden, Australian Capital Territory, Australia, 2606

Border Medical Oncology Research Unit

Albury, New South Wales, Australia, 2640

Concord Repatriation General Hospital

Concord, New South Wales, Australia, 2139

Liverpool Hospital

Liverpool, New South Wales, Australia, 2170

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

Sydney, New South Wales, Australia, 2217

Gold Coast University Hospital

Southport, Queensland, Australia, 4215

Monash University, Eastern Health-Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Northern Health

Epping, Victoria, Australia, 3076

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia, 3000

Ordensklinikum Linz GmbH Elisabethinen

Linz, Austria

Hanusch Krankenhaus

Vienna, Austria, 1140

Wiener Gesundheitsverbund, Klinik Hietzing

Wien, Austria, 1130

Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg

Antwerp, Belgium, 2060

Cliniques Universitaires Saint-Luc

Brussels, Belgium, 1200

University Hospital Gent

Gent, Belgium, 9000

Hopital de Jolimont

Haine-Saint-Paul, Belgium, 7100

University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg

Leuven, Belgium, 3000

Centre Hospitalier Universitaire de Liege

Liege, Belgium, 4000

Queen Elizabeth II (QEII) Health Sciences Centre

Halifax, Canada, B3H 1V7

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

Montreal, Canada, H1T 2M4

Princess Margaret Cancer Centre - University Health Network

Toronto, Canada, M5G 2M9

CancerCare Manitoba

Winnipeg, Canada, R3E 0V9

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

Jihormoravsky KRAJ, Czechia, 625 00

Fakultni nemocine Olomouc, Hemato-onkologicka klinika

Olomouc, Czechia, 77520

Fakultni nemocnice Ostrava, Klinika hematoonkologie

Ostrava, Czechia, 70852

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

Prague, Czechia, 100 34

Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance

Praha 2, Czechia, 128 08

CHU Amiens Picardie

Amiens Cedex 1, France, 80054

CHU d'Angers

Angers, France, 49033

Hopital Avicenne

Bobigny, France, 93000

Hopitaux Universitaires Henri Mondor

Creteil, France, 94010

Centre Hospitalier Universitaire Grenoble Alpes

La Tronche, France, 38700

Centre Hospitalier de Versailles

Le Chesnay Cedex, France, 78157

Hôpital Claude Huriez (CHRU de Lillle)

Lille Cedex, France, 59037

Centre Leon Berard

Lyon Cedex 08, France, 69373

Centre Hospitalier Universitaire Nantes - Hotel Dieu

Nantes, France, 44093

Hopital Saint-Louis

Paris, France, 75010

Centre Hospitalier Lyon-Sud (CHLS)

Pierre-Bénite, France, 69495

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, France, 67033

Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole

Toulouse, France, 31059

CHU de Nancy - Hopitaux de Brabois

Vandoeuvre-les-Nancy, France, 54500

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

Berlin, Germany, 13353

Universitätsklinikum Bonn

Bonn, Germany, 53127

Städtisches Klinikum Braunschweig GmbH Medizinische Klinik III/Hämatologie und Onkologie

Braunschweig, Germany, 38114

Universitatsklinikum Dusseldorf, Klink fur Hamatologie, Onkologie und Klinische Immunologie

Dusseldorf, Germany, 40225

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

Düsseldorf, Germany, 40479

Malteser Krankenhaus St. Franziskus Hospital,Med.Klinik I

Flensburg, Germany, 24939

Universitatsklinikum Frankfurt Goethe Universitat Med. Klink II

Frankfurt, Germany, 60590

Asklepios Klink St.Georg

Hamburg, Germany, 20099

Medizinische Hochschule Hannover, Hamatologie, Hamostaseologie, Onkologie und Stammzelltrandsplantation

Hannover, Germany, 30625

Universitätsklinikum Magdeburg

Magdeburg, Germany, 39120

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

Minden, Germany, 32429

Klinikum rechts der Isar Technischen Universitat Munchen

Muenchen, Germany, 81675

Klinikum Oldenburg, Rahel-Straus-Straße 10

Oldenburg, Germany, 26133

Universitatsklinikum Regensburg, Klink fur Innere Medizin III

Regensburg, Germany, 93053

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

Ulm, Germany, 89070

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

Hong Kong, Hong Kong

Princess Margaret Hospital

Hong Kong, Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong

Tuen Mun Hospital

Hong Kong, Hong Kong

Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika

Budapest, Hungary, 1083

Petz Aladár Egyetemi Oktató Kórház II. Belgyógyaszat - Haematológia

Gyor, Hungary, 9024

Debreceni Egyetem Klinikai Központ Belgyogyaszati Klinika B epulet Hematologia

Hajdu-bihar, Hungary, 4032

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Kozpont

Szeged, Hungary, 6725

Rambam Health Care Campus

Haifa, Israel, 31096

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Hadassah University Hospital Ein Kerem

Jerusalem, Israel, 91120

Rabin Medical Center

Petah Tikva, Israel, 49100

The Chaim Sheba Medical Center

Ramat Gan, Israel, 52621

Azienda Ospedaliero Universitaria delle Marche - SOD Clinica di Ematologia

Ancona, Italy, I-60126

ASST Papa Giovanni XXIII

Bergamo, Italy, 24127

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, Italy, 40138

IRCCS Istituto Clinico Humanitas

Milano, Italy, 20089

ASST Monza-Ospedale San Gerardo

Monza, Italy, 20052

Azienda Ospedaliera di Perugia - Santa Maria della Misericordia

Perugia, Italy

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

Pesaro, Italy, 61122

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Severance Hospital

Seoul, Korea, Republic of, 120-752

Asan Medical Center

Seoul, Korea, Republic of, 138-736

The Catholic University of Korea Seoul Saint Mary's Hospital

Seoul, Korea, Republic of, 6591

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands, 5223GZ

Meander Medisch Centrum

Amersfoort, Netherlands, 3813 TZ

Amsterdam Universitair Medische Centra-Locatie Vrije Universiteit Medisch Centrum

Amsterdam, Netherlands, 1081 HV

Amphia Hospital, department Oncologie, Route 43

Breda, Netherlands, 4818 CK

HagaZiekenhuis

Den Haag, Netherlands, 2545AA

Medisch Spectrum Twente - Enschede Koningsplein

Enschede, Netherlands, 7512 KZ

Universitair Medisch Centrum Groningen

Groningen, Netherlands, 9700 RB

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands, 8934 AD

Masstricht Universitair Medisch Centrum

Maastricht, Netherlands, 62002

St. Antonius Ziekenhuis, Nieuwegein

Nieuwegein, Netherlands, 3435 CM

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands, 6532 SZ

Erasmus Medisch Centrum

Rotterdam, Netherlands, 3000 CA

Oslo University Hospital, Department of Hematology

Oslo, Norway, 0424

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

Lublin, Poland, 20090

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

Opole, Poland, 45-372

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

Łódź, Poland, 93-510

Hospital Universitario Araba

Alava, Spain

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Hospital Universitario Reina Sofia

Cordoba, Spain, 14004

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28009

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28041

Hospital Universitario Quironsalud Madrid

Madrid, Spain

Hospital Universitario Ramon y Cajal

Madrid, Spain

Hospital Regional Universitario de Malaga

Malaga, Spain, 29010

Complejo Asistencial Universitario de Salamanca - Hospital Clinico

Salamanca, Spain, 37007

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, Spain, 15706

Hospital Universitari I Politecnic La Fe

Valencia, Spain, 46026

Inselspital Universitätsspital Bern

Berne, Switzerland, 3010

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung, Taiwan, 83301

China Medical University Hospital

Taichung, Taiwan, 404

National Taiwan University Hospital

Taipei, Taiwan, 10002

National Cheng Kung University Hospital

Taipei, Taiwan, 11490

Blackpool Teaching Hospitals NHS Foundation Trust

Blackpool, United Kingdom, FY3 8NR

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, United Kingdom, BS2 8ED

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom, LS9 7TF

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom, L7 8YA

Barts Health NHS Trust

London, United Kingdom, EC1A 7BE

King's College Hospital

London, United Kingdom, SE5 9RS

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Newcastle upon Tyne Hospitals Foundation Trust

Newcastle upon Tyne, United Kingdom, NE7 7DN

Oxford University Hospitals NHS Foundation Trust, Churchill Hospital

Oxford, United Kingdom, OX3 7LE

South Warwickshire University NHS Foundation Trust

Warwick, United Kingdom, CV34 5BW

The Royal Wolverhampton NHS Trust

Wolverhampton, United Kingdom, WV10 0QP

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

OVERVIEW

PROTOCOL SUMMARY

Participation Requirements

Eligibility Information

Inclusion Criteria

Exclusion Criteria

Locations

Locations (164)

University of Arkansas for Medical Sciences

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

Community Cancer Institute

UC Irvine Health- Chao Family Comprehensive Cancer Center

Baptist MD Anderson Cancer Center

Moffitt Cancer Center

Loyola University Medical Center

Parkview Research Center

Indiana Blood and Marrow Transplantation - Clinic

The University of Iowa Hospitals and Clinics

University of Maryland, Greenebaum Comprehensive Cancer Center

University of Massachusetts Worcester

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

SSM Health Saint Louis University Hospital

John Theurer Cancer Center at Hackensack University Medical Center

Rutgers Cancer Institute of New Jersey

New York-Presbyterian/Weill Cornell Medical Center

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

University of Rochester Medical Center

UNC Hospitals, The University of North Carolina at Chapel Hill

Novant Health Cancer Institute Hematology- Charlotte

Novant Health Cancer Institute Hematology - Forsyth

Wake Forest Baptist Health

University Hospitals Cleveland Medical Center

Cleveland Clinic Foundation

OU Health Stephenson Cancer Center

Providence Cancer Institute Franz Clinic

Penn State Hershey Medical Center

Fox Chase Cancer Center

West Penn Hospital

Rhode Island Hospital

Baylor University Medical Center

Brooke Army Medical Center

Houston Methodist Hospital Cancer Center

MD Anderson Cancer Center

Intermountain Health - LDS Hospital

Virginia Mason Franciscan Health

Fred Hutchinson Cancer Center

Froedtert Hospital and the Medical College of Wisconsin

Canberra Hospital

Border Medical Oncology Research Unit

Concord Repatriation General Hospital

Liverpool Hospital

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

Gold Coast University Hospital

Monash University, Eastern Health-Box Hill Hospital

Northern Health

Peter MacCallum Cancer Centre

Ordensklinikum Linz GmbH Elisabethinen

Hanusch Krankenhaus

Wiener Gesundheitsverbund, Klinik Hietzing

Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg

Cliniques Universitaires Saint-Luc

University Hospital Gent

Hopital de Jolimont

University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg

Centre Hospitalier Universitaire de Liege

Queen Elizabeth II (QEII) Health Sciences Centre

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

Princess Margaret Cancer Centre - University Health Network

CancerCare Manitoba

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

Fakultni nemocine Olomouc, Hemato-onkologicka klinika

Fakultni nemocnice Ostrava, Klinika hematoonkologie

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

Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance

CHU Amiens Picardie

CHU d'Angers

Hopital Avicenne

Hopitaux Universitaires Henri Mondor