Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)

NCT04313881 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 5F90092020-004287-26
• Study Type: interventional
• Target: 539
• Locations: 20 countries
• Sites: 167

Brief Summary

The primary objective of this study is to evaluate the efficacy of magrolimab in combination with azacitidine compared to that of azacitidine plus placebo in previously untreated participants with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R) as measured by complete remission (CR) and overall survival (OS).

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Complete Remission (CR)

  The percentage of participants (CR rate) are participants who reach morphologic CR (morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast) based on Investigator-assessed International Working Group (IWG) myelodysplastic syndrome (MDS) criteria on or prior to initiation of any new anticancer therapy, including stem cell therapy (SCT). Percentages were rounded off.

  From randomization up to 31.01 months

• Overall Survival (OS)

  OS is defined as the number of months measured from the date of randomization to the date of death from any cause. Kaplan Meier (KM) estimates were used for analysis.

  From randomization up to 32.62 months

Secondary Outcomes (13)

• Duration of CR (DOCR)

  From randomization up to 31.01 months

• Objective Response Rate (ORR)

  From randomization up to 31.01 months

• Duration of Response (DOR)

  From randomization up to 31.01 months

• Red Blood Cell (RBC) Transfusion Independence Rate

  From randomization up to 31.01 months

• Event Free Survival (EFS)

  From randomization up to 31.01 months

Study Arms (2)

Magrolimab + Azacitidine

EXPERIMENTAL

Participants will receive the following magrolimab and azacitidine dosing regimens: Magrolimab: Magrolimab Priming Dose: * 1 mg/kg on Days 1 and 4 * 15 mg/kg on Day 8 * 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Magrolimab Maintenance Dose: * 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle.

Drug: Magrolimab; Drug: Azacitidine

Control Arm (Placebo + Azacitidine)

PLACEBO COMPARATOR

Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo: On Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle.

Drug: Azacitidine; Drug: Placebo

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: Hu5F9-G4, GS-4721

Magrolimab + Azacitidine

Azacitidine DRUG

Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling

Control Arm (Placebo + Azacitidine); Magrolimab + Azacitidine

Placebo DRUG

Placebo to match magrolimab administered intravenously

Control Arm (Placebo + Azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
• Adequate performance status and hematological, liver, and kidney function.

You may not qualify if:

• Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor.
• Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
• Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R.
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year.
• Contraindications to azacitidine.
• Clinical suspicion of active central nervous system (CNS) involvement by MDS.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history .
• Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening.
• Pregnancy or active breastfeeding.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (169)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Arkansas for Medical Sciences IRB

Little Rock, Arkansas, 72205, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Ronald Reagan Medical Center

Los Angeles, California, 90095, United States

Location

UC Irvine Health

Orange, California, 92868, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical School

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mid America Division, Inc.

Kansas City, Missouri, 64132, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medicine-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

DUHS Duke Cancer Center

Durham, North Carolina, 27705, United States

Location

The Ohio State University Wexner Medical Center / James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University Pharmacy Services

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

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

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Prisma Health Cancer Center

Greenville, South Carolina, 29615, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 39090, United States

Location

Texas Oncology - Baylor Charles A. Simmons Cancer Center

Dallas, Texas, 75246, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98019, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Icon Cancer Foundation

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Center

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Peninsula Private Hospital

Frankston, Victoria, 3199, Australia

Location

Barwon Health, University Hospital Geelong

Geelong, Victoria, 3220, Australia

Location

Cabrini Hospital Malvern

Malvern, Victoria, 3144, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Uniklinikum Salzburg

Salzburg, 5020, Austria

Location

Hanusch kranhenkaus, 3. Medizinische Abteilung

Vienna, 1140, Austria

Location

ZNA Middelheim

Antwerp, 2060, Belgium

Location

ULB Hopital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Brussel

Brussels, Belgium

Location

Chu Ucl Namur Site Godinne

Godinne, 5530, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

AZ Turnhout, Campus St. Elisabeth

Turnhout, 2300, Belgium

Location

Tom Baker Cancer Centre

Calgary, T2N 4N2, Canada

Location

QEII Health Sciences Centre

Halifax, B3H 2Y9, Canada

Location

Eastern Regional Health Authority

St. John's, A1B 3V6, Canada

Location

University Health Network

Toronto, M5G 2M9, Canada

Location

Fakultni nemocnice Olomouc, Hemato-onkologicka klinika

Olomouc, 77520, Czechia

Location

Fakultni nemocnice Ostrava, Klinika hemato-onkologicka

Ostrava, 70852, Czechia

Location

Helsinki University Central Hospital

Helsinki, 00290, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

CHU Amiens-Picardie

Amiens, 80054, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble Alpes

La Tronche, 38700, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

CHU de Nantes

Nantes, 44000, France

Location

CHU de Nice-l Archet

Nice, 6200, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Institut Gustave Roussy

Paris, 94805, France

Location

Hopital Haut-Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers - Hopital de la Miletrie

Poitiers, 86000, France

Location

CHU de Rennes- Hopital Pontchaillou

Rennes, 35033, France

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz, III. Medizinische Klinik und Poliklinik

Braunschweig, 38114, Germany

Location

Universitatsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Marien hospital, klinik fur onkologie, hamatologie und palliavmedizin

Düsseldorf, Germany

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Universitat Leipzig

Leipzig, Germany

Location

Robert-Bosch-Krankenhaus, GmBH, Hamatologie, Onkologie und Palliativmedizin

Stuttgart, 70376, Germany

Location

Hong Kong Sanatorium & Hospital

Hong Kong, Hong Kong

Location

Princess Margaret Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Semmelweis Egyetem Belgyógyászati és Hematológiai Kilnika

Budapest, 1125, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

Petz Aladar Egyetemi Oktato Korhaz II. Belgyogyaszat - Hematologial Osztaly

Győr, 9024, Hungary

Location

Kaposi Mor Teaching Hospital

Kaposvár, Hungary

Location

Bács-Kiskun Megyei Kórház

Kecskemét, 6000, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

University of Pecs

Pécs, 7624, Hungary

Location

Szent Borbála Hospital

Tatabánya, 2800, Hungary

Location

SC Ematologica- Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo

Alessandria, 15100, Italy

Location

U.O Ematologica- ASST degli Spedali Civili di Brescia

Brescia, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

U.O.C Ematologia - Dipartimento di Medicina Interna, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

U.O di Ematologia, Ospedale San Gerardo- ASST Monza

Monza, 20052, Italy

Location

S. C. Ematologia Azienda Ospedaliero - Universitaria Maggiore Della Carita

Novara, 28100, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, 61100, Italy

Location

SC di Oncoematologia - Azienda Ospedaliera Santa Maria

Terni, 05100, Italy

Location

SC Ematologica, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Southern District Health Board

Dunedin, 9016, New Zealand

Location

Auckland City Hospital

Grafton, 1142, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Midcentral District Health Board

Palmerston North, 4414, New Zealand

Location

Haukeland Universitetssjukehus, seksjon for blodsjukdommar- klinisk studieteam

Bergen, 5021, Norway

Location

Akershus University Hospital

Loerenskog, 1478, Norway

Location

Oslo University Hospital

Oslo, 0372, Norway

Location

Stavanger universitetssjukehus

Stavanger, 4068, Norway

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Hematologii

Krakow, 31-501, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

Lublin, 20090, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, 50-367, Poland

Location

Centro Clinico Academico de Braga, Hospital de Braga, E.P.E

Braga, 4710, Portugal

Location

Champalimaud Foundation

Lisbon, 1400 - 038, Portugal

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Centro Hospitalar Universitario Sao Joao. E.P.E

Porto, 4200 319, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

Location

Centro Hospitalar Vila Nova de Gaia/Espinho

Porto, 4430-999, Portugal

Location

Area Sanitaria de Santiago de Compostela y Barbanza. Complejo Hospitalario Universitario de SantiagoD

A Coruña, Spain

Location

OSI Araba, Hospital Universitario de Alava, Hospital Txagorritxu

Alava, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d'Oncologia Girona

Girona, 17007, Spain

Location

Institut Catala d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz, Edificio General, 6 Planta. Despacho de Hematologia

Madrid, 28046, Spain

Location

Hospital Universitario Quironsalud Madrid. Servico de Hematologica y Hemoterapia

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Centro Hospitalar Universitario Sao Joao

Pamplona, 31008, Spain

Location

Complejo Asistencial Universitario de Salamanca- Hospital Clinico Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Istituto Oncologico Della Svizzera Italiana- IOSI, EOC, Clinica di Ematologia

Bellinzona, 6500, Switzerland

Location

University of Bern

Bern, 3010, Switzerland

Location

Universitaetsspital Zurich - Klinik fur Medizinische Onkologie und Hematologie

Zurich, 8091, Switzerland

Location

Hematoloji Bilim Dali, Yenimahalle

Ankara, 06200, Turkey (Türkiye)

Location

Gazi Universitesi Tip Fakultesi

Ankara, 06560, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Cebeci Hastanesi

Ankara, 06620, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi Onkoloji Enstitusu

Inciralt, 35340, Turkey (Türkiye)

Location

Mersin University Medical

Mersin, 33110, Turkey (Türkiye)

Location

Tekirdag Namik Kemal Universitesi Tip Fakultesi

Tekirdağ, 59100, Turkey (Türkiye)

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

United Lincolnshire Hospital NHS Trust

Boston, PE21 9QS, United Kingdom

Location

Kent and Canterbury Hospital- East Kent Hospitals University NHS Foundation Trust

Canterbury, CT1 3NG, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (1)

• Sallman DA, Al Malki MM, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN, Zeidner JF, Garcia-Manero G, Jeyakumar D, Komrokji R, Lancet J, Kantarjian HM, Gu L, Zhang Y, Tan A, Chao M, O'Hear C, Ramsingh G, Lal I, Vyas P, Daver NG. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study. J Clin Oncol. 2023 May 20;41(15):2815-2826. doi: 10.1200/JCO.22.01794. Epub 2023 Mar 8.

  PMID: 36888930 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

magrolimab; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 18, 2020
• Study Start: September 9, 2020
• Primary Completion: September 13, 2023
• Study Completion: September 13, 2023
• Last Updated: June 27, 2024
• Results First Posted: March 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (3); NL (2); CA (4); DE (6); IT (9); US (47); AU (16); FR (13); NO (4); CZ (2); PT (6); FI (2); BE (7); TU (6); GB (4); HK (5); ES (15); NZ (5); PL (3); HU (8)