Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) (ENHANCE)
Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes
Eligibility Criteria
Key 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
Key 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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- University of Alabama Birmingham
- University of Arkansas for Medical Sciences IRB
- City of Hope
- UC San Diego Moores Cancer Center
- UCLA Ronald Reagan Medical Center
- UC Irvine Health
- Stanford Cancer Institute
- University of California, Davis Comprehensive Cancer Center
- University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center
- Moffitt Cancer Center
- Winship Cancer Institute
- Northwestern Memorial Hospital
- The University of Chicago Medical Center
- University of Kansas Clinical Research Center
- Tulane Medical Center
- University of Maryland, Greenebaum Comprehensive Cancer Center
- Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute (DFCI)
- University of Michigan Medical School
- University of Minnesota Medical Center, Fairview
- Mid America Division, Inc.
- Washington University School of Medicine - Siteman Cancer Center
- Roswell Park Cancer Institute
- Weill Cornell Medicine-New York Presbyterian Hospital
- Mount Sinai Health System
- Columbia University Medical Center - Herbert Irving Pavilion
- Memorial Sloan Kettering Cancer Center
- University of North Carolina at Chapel Hill
- DUHS Duke Cancer Center
- The Ohio State University Wexner Medical Center / James Cancer Hospital
- University of Oklahoma Health Sciences Center
- Oregon Health & Science University Pharmacy Services
- Hospital of the University of Pennsylvania
- Thomas Jefferson University, Sidney Kimmel Cancer Center; Clinical Research Organization
- Fox Chase Cancer Center
- Prisma Health Cancer Center
- Tennessee Oncology, PLLC
- UT Southwestern Medical Center
- Texas Oncology - Baylor Charles A. Simmons Cancer Center
- Baylor College of Medicine
- The University of Texas MD Anderson Cancer Center
- Huntsman Cancer Institute/University of Utah
- Seattle Cancer Care Alliance
- Swedish Cancer Institute
- Froedtert Hospital & the Medical College of Wisconsin
- Gosford Hospital
- Prince of Wales Hospital
- Royal North Shore Hospital
- Westmead Hospital
- Icon Cancer Foundation
- Royal Adelaide Hospital
- Flinders Medical Center
- Royal Hobart Hospital
- Eastern Health
- Monash Medical Centre
- Peninsula Private Hospital
- Barwon Health, University Hospital Geelong
- Cabrini Hospital Malvern
- The Alfred Hospital
- Royal Melbourne Hospital
- Sir Charles Gairdner Hospital
- Uniklinikum Salzburg
- Hanusch kranhenkaus, 3. Medizinische Abteilung
- ZNA Middelheim
- ULB Hopital Erasme
- Cliniques Universitaires Saint-Luc
- UZ Brussel
- UZ Leuven
- AZ Turnhout, Campus St. Elisabeth
- Chu Ucl Namur Site Godinne
- Tom Baker Cancer Centre
- QEII Health Sciences Centre
- Eastern Regional Health Authority
- University Health Network
- Fakultni nemocnice Olomouc, Hemato-onkologicka klinika
- Fakultni nemocnice Ostrava, Klinika hemato-onkologicka
- Helsinki University Central Hospital
- Oulu University Hospital
- CHU Amiens-Picardie
- Hopital Henri Mondor
- CHU de Grenoble Alpes
- Institut Paoli Calmettes
- Hopital Saint Eloi
- CHU de Nantes
- CHU de Nice-l Archet
- Hopital Saint Louis
- Institut Gustave Roussy
- Hopital Haut-Leveque
- Centre Hospitalier Lyon Sud
- CHU de Poitiers - Hopital de la Miletrie
- CHU de Rennes- Hopital Pontchaillou
- Universitatsmedizin der Johannes Gutenberg Universitat Mainz, III. Medizinische Klinik und Poliklinik
- Universitatsklinikum Carl Gustav Carus
- Marien hospital, klinik fur onkologie, hamatologie und palliavmedizin
- Universitatsklinikum Essen
- Universitat Leipzig
- Robert-Bosch-Krankenhaus, GmBH, Hamatologie, Onkologie und Palliativmedizin
- Hong Kong Sanatorium & Hospital
- Princess Margaret Hospital
- Queen Mary Hospital
- The Chinese University of Hong Kong, Prince of Wales Hospital
- Tuen Mun Hospital
- Semmelweis Egyetem Belgyógyászati és Hematológiai Kilnika
- Debreceni Egyetem Klinikai Központ
- Petz Aladar Egyetemi Oktato Korhaz II. Belgyogyaszat - Hematologial Osztaly
- Kaposi Mor Teaching Hospital
- Bács-Kiskun Megyei Kórház
- SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
- University of Pecs
- Szent Borbála Hospital
- SC Ematologica- Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
- U.O Ematologica- ASST degli Spedali Civili di Brescia
- Azienda Ospedaliero-Universitaria Careggi
- U.O.C Ematologia - Dipartimento di Medicina Interna, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
- U.O di Ematologia, Ospedale San Gerardo- ASST Monza
- S. C. Ematologia Azienda Ospedaliero - Universitaria Maggiore Della Carita
- Azienda Ospedaliera Ospedali Riuniti Marche Nord
- SC di Oncoematologia - Azienda Ospedaliera Santa Maria
- SC Ematologica, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi
- University Medical Center Groningen
- Medisch Centrum Leeuwarden
- Christchurch Hospital
- Southern District Health Board
- Auckland City Hospital
- Waikato Hospital
- Midcentral District Health Board
- Haukeland Universitetssjukehus, seksjon for blodsjukdommar- klinisk studieteam
- Akershus University Hospital
- Oslo University Hospital
- Stavanger universitetssjukehus
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Hematologii
- Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
- Centro Clinico Academico de Braga, Hospital de Braga, E.P.E
- Champalimaud Foundation
- Hospital da Luz
- Centro Hospitalar Universitario Sao Joao. E.P.E
- Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
- Centro Hospitalar Vila Nova de Gaia/Espinho
- Area Sanitaria de Santiago de Compostela y Barbanza. Complejo Hospitalario Universitario de SantiagoD
- OSI Araba, Hospital Universitario de Alava, Hospital Txagorritxu
- Hospital del Mar
- Hospital Universitari Vall D'Hebron
- Institut Catala d'Oncologia Girona
- Institut Catala d'Oncologia, Hospital Duran i Reynals
- MD Anderson Cancer Center Madrid
- Hospital Universitario Fundacion Jimenez Diaz
- Hospital Universitario La Paz, Edificio General, 6 Planta. Despacho de Hematologia
- Hospital Universitario Quironsalud Madrid. Servico de Hematologica y Hemoterapia
- Hospital Regional Universitario de Malaga
- Centro Hospitalar Universitario Sao Joao
- Complejo Asistencial Universitario de Salamanca- Hospital Clinico Universitario de Salamanca
- Hospital Universitario Virgen del Rocio
- Hospital Clinico Universitario de Valencia
- Istituto Oncologico Della Svizzera Italiana- IOSI, EOC, Clinica di Ematologia
- University of Bern
- Universitaetsspital Zurich - Klinik fur Medizinische Onkologie und Hematologie
- Hematoloji Bilim Dali, Yenimahalle
- Gazi Universitesi Tip Fakultesi
- Ankara Universitesi Tip Fakultesi Cebeci Hastanesi
- Dokuz Eylul Universitesi Tip Fakultesi Onkoloji Enstitusu
- Mersin University Medical
- Tekirdag Namik Kemal Universitesi Tip Fakultesi
- University Hospitals Birmingham NHS Foundation Trust
- United Lincolnshire Hospital NHS Trust
- Kent and Canterbury Hospital- East Kent Hospitals University NHS Foundation Trust
- Oxford University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Magrolimab + Azacitidine
Control Arm (Placebo + 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
Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitadine: Placebo 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) Placebo 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 cycle