Clinical trial NCT04313881: Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
Official title: ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-03-18
Enrollment: 539
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Participants With Complete Remission (CR)
timeFrame: From randomization up to 31.01 months
measure: Overall Survival (OS)
timeFrame: From randomization up to 32.62 months
Secondary outcomes:
measure: Duration of CR (DOCR)
timeFrame: From randomization up to 31.01 months
measure: Objective Response Rate (ORR)
timeFrame: From randomization up to 31.01 months
measure: Duration of Response (DOR)
timeFrame: From randomization up to 31.01 months
measure: Red Blood Cell (RBC) Transfusion Independence Rate
timeFrame: From randomization up to 31.01 months
measure: Event Free Survival (EFS)
timeFrame: From randomization up to 31.01 months
measure: Percentage of Participants With CR in Participants With TP53 Mutation
timeFrame: From randomization up to 31.01 months
measure: Minimal Residual Disease (MRD)-Negative Response Rate
timeFrame: From randomization up to 31.01 months
measure: Time to Transformation to AML
timeFrame: From randomization up to 31.01 months
measure: Progression Free Survival (PFS)
timeFrame: From randomization up to 31.01 months
measure: Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate
timeFrame: Up to week 136
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
timeFrame: First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)
measure: Serum Concentration of Magrolimab
timeFrame: Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336
measure: Percentage of Participants With Positive Anti-magrolimab Antibodies
timeFrame: Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences IRB
state: Arkansas
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical School
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Kansas City
country: United States
facility: Mid America Division, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: DUHS Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center / James Cancer Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University Pharmacy Services
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center; Clinical Research Organization
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Center
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health, University Hospital Geelong
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg
city: Vienna
country: Austria
facility: Hanusch kranhenkaus, 3. Medizinische Abteilung
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: ULB Hopital Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Turnhout
country: Belgium
facility: AZ Turnhout, Campus St. Elisabeth
city: Yvoir-Godinne
country: Belgium
facility: Chu Ucl Namur Site Godinne
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
city: St. John's
country: Canada
facility: Eastern Regional Health Authority
city: Toronto
country: Canada
facility: University Health Network
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc, Hemato-onkologicka klinika
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava, Klinika hemato-onkologicka
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Amiens Cedex 1
country: France
facility: CHU Amiens-Picardie
city: Creteil
country: France
facility: Hopital Henri Mondor
city: La Tronche
country: France
facility: CHU de Grenoble Alpes
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice-l Archet
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Institut Gustave Roussy
city: Pessac Cedex
country: France
facility: Hopital Haut-Leveque
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers - Hopital de la Miletrie
city: Rennes Cedex 9
country: France
facility: CHU de Rennes- Hopital Pontchaillou
city: Braunschweig
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg Universitat Mainz, III. Medizinische Klinik und Poliklinik
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Marien hospital, klinik fur onkologie, hamatologie und palliavmedizin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Leipzig
country: Germany
facility: Universitat Leipzig
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus, GmBH, Hamatologie, Onkologie und Palliativmedizin
city: Hong Kong
country: Hong Kong
facility: Hong Kong Sanatorium & Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong, Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Belgyógyászati és Hematológiai Kilnika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
city: Gyor
country: Hungary
facility: Petz Aladar Egyetemi Oktato Korhaz II. Belgyogyaszat - Hematologial Osztaly
city: Kaposvar
country: Hungary
facility: Kaposi Mor Teaching Hospital
city: Kecskemet
country: Hungary
facility: Bács-Kiskun Megyei Kórház
city: Nyiregyhaza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
city: Pecs
country: Hungary
facility: University of Pecs
city: Tatabanya
country: Hungary
facility: Szent Borbála Hospital
city: Alessandria
country: Italy
facility: SC Ematologica- Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
city: Brescia
country: Italy
facility: U.O Ematologica- ASST degli Spedali Civili di Brescia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Milan
country: Italy
facility: U.O.C Ematologia - Dipartimento di Medicina Interna, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: U.O di Ematologia, Ospedale San Gerardo- ASST Monza
city: Novara
country: Italy
facility: S. C. Ematologia Azienda Ospedaliero - Universitaria Maggiore Della Carita
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
city: Terni
country: Italy
facility: SC di Oncoematologia - Azienda Ospedaliera Santa Maria
city: Varese
country: Italy
facility: SC Ematologica, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Southern District Health Board
city: Grafton
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Palmerston North
country: New Zealand
facility: Midcentral District Health Board
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus, seksjon for blodsjukdommar- klinisk studieteam
city: Loerenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger universitetssjukehus
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Hematologii
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Braga
country: Portugal
facility: Centro Clinico Academico de Braga, Hospital de Braga, E.P.E
city: Lisbon
country: Portugal
facility: Champalimaud Foundation
city: Lisbon
country: Portugal
facility: Hospital da Luz
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario Sao Joao. E.P.E
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia/Espinho
city: A Coruña
country: Spain
facility: Area Sanitaria de Santiago de Compostela y Barbanza. Complejo Hospitalario Universitario de SantiagoD
city: Alava
country: Spain
facility: OSI Araba, Hospital Universitario de Alava, Hospital Txagorritxu
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Girona
country: Spain
facility: Institut Catala d'Oncologia Girona
city: L´Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia, Hospital Duran i Reynals
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Edificio General, 6 Planta. Despacho de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid. Servico de Hematologica y Hemoterapia
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Pamplona
country: Spain
facility: Centro Hospitalar Universitario Sao Joao
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca- Hospital Clinico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico Della Svizzera Italiana- IOSI, EOC, Clinica di Ematologia
city: Bern
country: Switzerland
facility: University of Bern
city: Zurich
country: Switzerland
facility: Universitaetsspital Zurich - Klinik fur Medizinische Onkologie und Hematologie
city: Ankara
country: Turkey
facility: Hematoloji Bilim Dali, Yenimahalle
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Cebeci Hastanesi
city: Inciralt
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi Onkoloji Enstitusu
city: Mersin
country: Turkey
facility: Mersin University Medical
city: Tekirdag
country: Turkey
facility: Tekirdag Namik Kemal Universitesi Tip Fakultesi
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Boston
country: United Kingdom
facility: United Lincolnshire Hospital NHS Trust
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital- East Kent Hospitals University NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: