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

Myelodysplastic Syndromes Clinical Trial

— ENHANCE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04313881
• Other study ID #: 5F9009
• Secondary ID: 2020-004287-26
• Status: Terminated
• Phase: Phase 3
• Start date: September 9, 2020
• Est. completion date: September 13, 2023

Study information

• Verified date: March 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 539
• Est. completion date: September 13, 2023
• Est. primary completion date: September 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa)-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.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Magrolimab
Administered intravenously
• Azacitidine
Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling
• Placebo
Placebo to match magrolimab administered intravenously

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Duration of CR (DOCR)	DOCR=Time from first CR date to the first date of relapse, disease progression (PD) or death, whichever occurs earlier. PD is defined as: <5% blasts: =50 increase in blasts to >5% blasts,5%-10% blasts: =50% increase in blasts to >10% blasts, 10%-20% blasts: =50% increase in blasts to >20% blasts,20%-30% blasts: =50% increase in blasts to >30% blasts, any of the following: at least 50% decrement from maximum remission/response in granulocytes or platelets. Reduction in Hgb by =2 g/dL / Transfusion dependence. Relapse is defined as return to pretreatment bone marrow blast percentage / decrement of = 50% from maximum remission/response levels in granulocytes or platelets/ reduction in Hgb concentration by = 1.5 g/dL or transfusion dependence. CR is defined in outcome measure 1. KM estimates were used for analysis.	From randomization up to 31.01 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who reach objective response including CR, partial remission (PR), marrow CR or hematological improvement prior to initiation of any new anticancer therapy including SCT for MDS per IWG 2006 criteria per investigator's evaluation. CR is defined in outcome measure 1.; PR is defined as all CR criteria if abnormal before treatment except, one marrow blasts decreased by = 50% over pretreatment but still > 5% cellularity and morphology not relevant.; Marrow CR is defined as bone marrow = 5% myeloblasts and decrease by = 50% over pretreatment, stable disease with any hematological improvement, peripheral blood: if hematological improvement responses, they were noted in addition to marrow CR.; Stable Disease: Failure to achieve at least PR, but no evidence of progression for > 8 weeks.; Percentages were rounded off.	From randomization up to 31.01 months
Secondary	Duration of Response (DOR)	DOR is measured from time measurement criteria are first met for objective response to first date of relapse, disease progression (PD) /death, whichever occurs earlier.; Disease progression and relapse have been defined in outcome measure number 3. KM estimates were used for analysis.	From randomization up to 31.01 months
Secondary	Red Blood Cell (RBC) Transfusion Independence Rate	RBC transfusion independence rate is defined as the percentage of participants who have a 56-day or longer period with no RBC transfusions at any time between randomization and initiation of any new anticancer therapy, including SCT, among all participants who were RBC transfusion-dependent at Baseline. Percentages were rounded off.	From randomization up to 31.01 months
Secondary	Event Free Survival (EFS)	EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first.; Transformation assessments and deaths post SCT were included in the analysis. KM estimates were used for analysis	From randomization up to 31.01 months
Secondary	Percentage of Participants With CR Rate in Participants With TP53 Mutation	CR in TP53 mutant population is defined as the percentage of participants who achieve a morphologic CR based on investigator assessments using IWG criteria on or prior to initiation of any new anticancer therapy, including SCT in TP53 mutant population. Percentages were rounded off.	From randomization up to 31.01 months
Secondary	Minimal Residual Disease (MRD)-Negative Response Rate	The MRD-negative response rate is defined as the percentage of participants who achieved a morphologic CR or marrow CR based on Investigator-assessed IWG criteria and reached MRD-negative disease status prior to initiation of any new anticancer therapy, including SCT. MRD-negative disease status was assessed using a multiparameter flow cytometry-based assay performed by a central laboratory. Transformation assessments post SCT were to be included in the analysis.; Morphologic CR and marrow CR are defined in outcome measures 1 and 4, respectively.; Percentages were rounded off.	From randomization up to 31.01 months
Secondary	Time to Transformation to AML	Time to transformation to AML is defined as the time from randomization to the collection date of bone marrow sample leading to documented AML diagnosis. KM estimates were used for analysis.	From randomization up to 31.01 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from randomization to the date of documented DP (including treatment failure by IWG criteria or relapse after PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post SCT were included in the analysis.; CR, PR and PD are defined in outcome measures 1, 4 and 5 respectively. KM estimates were used for analysis.	From randomization up to 31.01 months
Secondary	Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate	The FACT-Anemia response rate is defined as the percentage of participants who showed clinically meaningful improvement in health-related quality of life (HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new anticancer therapy, including SCT. The minimal clinically meaningful difference of 7.0 was used as cutoff for clinically meaningful improvement.; The FACT-Anemia instrument consists of 5 subscales, including physical well-being, emotional well-being, functional well-being, social well-being, and anemia symptoms. Each subscale measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much. The subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest quality of life (QOL) and 100 denotes the highest QOL.; Percentages were rounded off.	Up to week 136
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events	Treatment-emergent adverse events (TEAEs) are defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dose date or the day before initiation of new anticancer therapy including SCT (whichever is earlier). If the AE onset date is on or before the last dose date, the AE is considered as TEAE regardless of the start of new anticancer therapy.; An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol imposed intervention, regardless of attribution.; An event is considered "serious", if it results in any of the following outcomes: death, life-threatening, inpatient or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, and important medical events.	First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)
Secondary	Serum Concentration of Magrolimab	Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected within 24 hours prior to study treatment administration.	Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336
Secondary	Percentage of Participants With Positive Anti-magrolimab Antibodies	Percentages were rounded off.	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

External Links

•   Gilead Clinical Trials Website