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

NCT ID: NCT04313881

Last Updated: 2024-06-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

539 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-09

Study Completion Date

2023-09-13

Brief Summary

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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).

Detailed Description

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Conditions

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Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Magrolimab + Azacitidine

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.

Group Type EXPERIMENTAL

Magrolimab

Intervention Type DRUG

Administered intravenously

Azacitidine

Intervention Type DRUG

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

Control Arm (Placebo + Azacitidine)

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.

Group Type PLACEBO_COMPARATOR

Azacitidine

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo to match magrolimab administered intravenously

Interventions

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Magrolimab

Administered intravenously

Intervention Type DRUG

Azacitidine

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

Intervention Type DRUG

Placebo

Placebo to match magrolimab administered intravenously

Intervention Type DRUG

Other Intervention Names

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Hu5F9-G4 GS-4721

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Alabama Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences IRB

Little Rock, Arkansas, United States

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City of Hope

Duarte, California, United States

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UC San Diego Moores Cancer Center

La Jolla, California, United States

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UCLA Ronald Reagan Medical Center

Los Angeles, California, United States

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UC Irvine Health

Orange, California, United States

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Stanford Cancer Institute

Palo Alto, California, United States

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University of California, Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center

Miami, Florida, United States

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Moffitt Cancer Center

Tampa, Florida, United States

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Winship Cancer Institute

Atlanta, Georgia, United States

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Northwestern Memorial Hospital

Chicago, Illinois, United States

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The University of Chicago Medical Center

Chicago, Illinois, United States

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University of Kansas Clinical Research Center

Fairway, Kansas, United States

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Tulane Medical Center

New Orleans, Louisiana, United States

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University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, United States

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University of Michigan Medical School

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Site Status

Mid America Division, Inc.

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

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Roswell Park Cancer Institute

Buffalo, New York, United States

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Weill Cornell Medicine-New York Presbyterian Hospital

New York, New York, United States

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Mount Sinai Health System

New York, New York, United States

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Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

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DUHS Duke Cancer Center

Durham, North Carolina, United States

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The Ohio State University Wexner Medical Center / James Cancer Hospital

Columbus, Ohio, United States

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University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

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Oregon Health & Science University Pharmacy Services

Portland, Oregon, United States

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Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

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

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Prisma Health Cancer Center

Greenville, South Carolina, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

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Texas Oncology - Baylor Charles A. Simmons Cancer Center

Dallas, Texas, United States

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Baylor College of Medicine

Houston, Texas, United States

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The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

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Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

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Seattle Cancer Care Alliance

Seattle, Washington, United States

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Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

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Gosford Hospital

Gosford, New South Wales, Australia

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Prince of Wales Hospital

Randwick, New South Wales, Australia

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Royal North Shore Hospital

St Leonards, New South Wales, Australia

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Westmead Hospital

Westmead, New South Wales, Australia

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Icon Cancer Foundation

South Brisbane, Queensland, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

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Flinders Medical Center

Bedford Park, South Australia, Australia

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Royal Hobart Hospital

Hobart, Tasmania, Australia

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Eastern Health

Box Hill, Victoria, Australia

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Monash Medical Centre

Clayton, Victoria, Australia

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Peninsula Private Hospital

Frankston, Victoria, Australia

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Barwon Health, University Hospital Geelong

Geelong, Victoria, Australia

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Cabrini Hospital Malvern

Malvern, Victoria, Australia

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The Alfred Hospital

Melbourne, Victoria, Australia

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Royal Melbourne Hospital

Parkville, Victoria, Australia

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Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

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Uniklinikum Salzburg

Salzburg, , Austria

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Hanusch kranhenkaus, 3. Medizinische Abteilung

Vienna, , Austria

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ZNA Middelheim

Antwerp, , Belgium

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ULB Hopital Erasme

Brussels, , Belgium

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Cliniques Universitaires Saint-Luc

Brussels, , Belgium

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UZ Brussel

Brussels, , Belgium

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Chu Ucl Namur Site Godinne

Godinne, , Belgium

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UZ Leuven

Leuven, , Belgium

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AZ Turnhout, Campus St. Elisabeth

Turnhout, , Belgium

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Tom Baker Cancer Centre

Calgary, , Canada

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QEII Health Sciences Centre

Halifax, , Canada

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Eastern Regional Health Authority

St. John's, , Canada

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University Health Network

Toronto, , Canada

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Fakultni nemocnice Olomouc, Hemato-onkologicka klinika

Olomouc, , Czechia

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Fakultni nemocnice Ostrava, Klinika hemato-onkologicka

Ostrava, , Czechia

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Helsinki University Central Hospital

Helsinki, , Finland

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Oulu University Hospital

Oulu, , Finland

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CHU Amiens-Picardie

Amiens, , France

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Hopital Henri Mondor

Créteil, , France

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CHU de Grenoble Alpes

La Tronche, , France

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Institut Paoli Calmettes

Marseille, , France

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Hopital Saint Eloi

Montpellier, , France

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CHU de Nantes

Nantes, , France

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CHU de Nice-l Archet

Nice, , France

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Hopital Saint Louis

Paris, , France

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Institut Gustave Roussy

Paris, , France

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Hopital Haut-Leveque

Pessac, , France

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Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

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CHU de Poitiers - Hopital de la Miletrie

Poitiers, , France

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CHU de Rennes- Hopital Pontchaillou

Rennes, , France

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

Braunschweig, , Germany

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Universitatsklinikum Carl Gustav Carus

Dresden, , Germany

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Marien hospital, klinik fur onkologie, hamatologie und palliavmedizin

Düsseldorf, , Germany

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Universitatsklinikum Essen

Essen, , Germany

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Universitat Leipzig

Leipzig, , Germany

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

Stuttgart, , Germany

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Hong Kong Sanatorium & Hospital

Hong Kong, , Hong Kong

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Princess Margaret Hospital

Hong Kong, , Hong Kong

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Queen Mary Hospital

Hong Kong, , Hong Kong

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The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, , Hong Kong

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Tuen Mun Hospital

Hong Kong, , Hong Kong

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Semmelweis Egyetem Belgyógyászati és Hematológiai Kilnika

Budapest, , Hungary

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Debreceni Egyetem Klinikai Központ

Debrecen, , Hungary

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Petz Aladar Egyetemi Oktato Korhaz II. Belgyogyaszat - Hematologial Osztaly

Győr, , Hungary

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Kaposi Mor Teaching Hospital

Kaposvár, , Hungary

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Bács-Kiskun Megyei Kórház

Kecskemét, , Hungary

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SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

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University of Pecs

Pécs, , Hungary

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Szent Borbála Hospital

Tatabánya, , Hungary

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

Alessandria, , Italy

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U.O Ematologica- ASST degli Spedali Civili di Brescia

Brescia, , Italy

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Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

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

Milan, , Italy

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

Monza, , Italy

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

Novara, , Italy

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Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, , Italy

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SC di Oncoematologia - Azienda Ospedaliera Santa Maria

Terni, , Italy

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

Varese, , Italy

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University Medical Center Groningen

Groningen, , Netherlands

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Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

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Christchurch Hospital

Christchurch, , New Zealand

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Southern District Health Board

Dunedin, , New Zealand

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Auckland City Hospital

Grafton, , New Zealand

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Waikato Hospital

Hamilton, , New Zealand

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Midcentral District Health Board

Palmerston North, , New Zealand

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Haukeland Universitetssjukehus, seksjon for blodsjukdommar- klinisk studieteam

Bergen, , Norway

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Akershus University Hospital

Loerenskog, , Norway

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Oslo University Hospital

Oslo, , Norway

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Stavanger universitetssjukehus

Stavanger, , Norway

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

Krakow, , Poland

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Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

Lublin, , Poland

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Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, , Poland

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

Braga, , Portugal

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Champalimaud Foundation

Lisbon, , Portugal

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Hospital da Luz

Lisbon, , Portugal

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Centro Hospitalar Universitario Sao Joao. E.P.E

Porto, , Portugal

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Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, , Portugal

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Centro Hospitalar Vila Nova de Gaia/Espinho

Porto, , Portugal

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

A Coruña, , Spain

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OSI Araba, Hospital Universitario de Alava, Hospital Txagorritxu

Alava, , Spain

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Hospital del Mar

Barcelona, , Spain

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Hospital Universitari Vall D'Hebron

Barcelona, , Spain

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Institut Catala d'Oncologia Girona

Girona, , Spain

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Institut Catala d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

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MD Anderson Cancer Center Madrid

Madrid, , Spain

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Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

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

Madrid, , Spain

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Hospital Universitario Quironsalud Madrid. Servico de Hematologica y Hemoterapia

Madrid, , Spain

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Hospital Regional Universitario de Malaga

Málaga, , Spain

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Centro Hospitalar Universitario Sao Joao

Pamplona, , Spain

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Complejo Asistencial Universitario de Salamanca- Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

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Hospital Clinico Universitario de Valencia

Valencia, , Spain

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

Bellinzona, , Switzerland

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University of Bern

Bern, , Switzerland

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Universitaetsspital Zurich - Klinik fur Medizinische Onkologie und Hematologie

Zurich, , Switzerland

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Hematoloji Bilim Dali, Yenimahalle

Ankara, , Turkey (Türkiye)

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Gazi Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

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Ankara Universitesi Tip Fakultesi Cebeci Hastanesi

Ankara, , Turkey (Türkiye)

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Dokuz Eylul Universitesi Tip Fakultesi Onkoloji Enstitusu

Inciralt, , Turkey (Türkiye)

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Mersin University Medical

Mersin, , Turkey (Türkiye)

Site Status

Tekirdag Namik Kemal Universitesi Tip Fakultesi

Tekirdağ, , Turkey (Türkiye)

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University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

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United Lincolnshire Hospital NHS Trust

Boston, , United Kingdom

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

Canterbury, , United Kingdom

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Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia Finland France Germany Hong Kong Hungary Italy Netherlands New Zealand Norway Poland Portugal Spain Switzerland Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 36888930 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: First Interim Analyses

View Document

Document Type: Statistical Analysis Plan: Second Interim and Final Analyses

View Document

Related Links

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Other Identifiers

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2020-004287-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5F9009

Identifier Type: -

Identifier Source: org_study_id

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