Clinical trial NCT05079230: Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-10-15
Enrollment: 378
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 goal of this clinical study is to compare the study drugs, magrolimab + venetoclax + azacitidine, versus placebo + venetoclax + azacitidine in participants with untreated acute myeloid leukemia (AML) who are not able to have chemotherapy.


Eligibility criteria: Key Inclusion Criteria:

* Previously untreated individuals with histological confirmation of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Individuals must be considered ineligible for intensive chemotherapy, defined by the following:

  * ≥ 75 years of age; Or
  * ≥ 18 to 74 years of age with at least 1 of the following comorbidities:

    * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
    * Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
    * Left ventricular ejection fraction ≤ 50%
    * Baseline creatinine clearance ≥ 30 mL/min to \< 45 mL/min calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
    * Hepatic disorder with total bilirubin \> 1.5 x upper limit of normal (ULN)
    * Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
  * ECOG performance status:

    * Of 0 to 2 for individuals ≥ 75 years of age Or
    * Of 0 to 3 for individuals ≥ 18 to 74 years of age
* Individuals with white blood cell (WBC) count ≤ 20 x 10\^3/μL prior to randomization. If the individual's WBC is \> 20 x10\^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20 x 10\^3/μL prior to the first dose of study treatment and prior to each magrolimab/placebo dose during Cycle 1.

  * Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to randomization and throughout the study to reduce the WBC to ≤ 20 x 10\^3/μL to enable eligibility for study drug dosing
* Hemoglobin must be ≥ 9 g/dL prior to initial dose of study treatment

  * Note: Transfusions are allowed to meet hemoglobin eligibility
* Pretreatment blood cross-match completed

Key Exclusion Criteria:

* Prior treatment with any of the following:

  * cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα)-targeting agents
  * Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea

    * Note: Individuals with prior MDS who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS may be enrolled in the study. Prior treatment with myelodysplastic syndrome (MDS) therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell negative (RBC-), white blood cell negative (WBC-), or platelet-direct therapies or growth factors is allowed for these individuals.
* Clinical suspicion of or documented active central nervous system (CNS) involvement with AML
* Individuals who have acute promyelocytic leukemia
* Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 1.6 years
Secondary outcomes:
measure: Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)
timeFrame: Up to 1.6 years
measure: Rate of Complete Remission (CR)
timeFrame: Up to 1.6 years
measure: Event-Free Survival (EFS)
timeFrame: Up to 1.6 years
measure: Duration of CR + CRh in Participants Who Achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)
timeFrame: Up to 1.6 years
measure: Duration of Complete Remission (DCR) in Participants Who Achieved Complete Remission (CR)
timeFrame: Up to 1.6 years
measure: Rate of CR/CRh Without Minimal Residual Disease (CR/CRhMRD-)
timeFrame: Up to 1.6 years
measure: Rate of CR Without Minimal Residual Disease (CRMRD-)
timeFrame: Up to 1.6 years
measure: Red Blood Cell (RBC) Transfusion Independence Conversion Rate
timeFrame: Up to 1.6 years
measure: Platelet Transfusion Independence Conversion Rate
timeFrame: Up to 1.6 years
measure: Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale
timeFrame: Up to 1.6 years
measure: Time to First Deterioration (TTD) on the EORTC QLQ-C30 Physical Functioning Scale
timeFrame: Up to 1.6 years
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 1.4 years plus 70 days
measure: Percentage of Participants Experiencing Grade 3 or Higher Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to 1.4 years, plus 70 days
measure: Serum Concentration of Magrolimab Over Time
timeFrame: Predose on Day 1, Day 8, Day 15, Day 29; Predose on Day 57 and 1 hour post-dose; Predose on Day 113, Day 169, Day 253, and Day 337.
measure: Percentage of Participants With Anti-Magrolimab Antibodies
timeFrame: Up to 1.6 years
measure: Maximum Levels of Serum Anti-Magrolimab Antibodies
timeFrame: Up to 1.6 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Fresno
country: United States
facility: Community Cancer Institute
state: California
city: Orange
country: United States
facility: UC Irvine Health- Chao Family Comprehensive Cancer Center
state: California
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation - Clinic
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Kansas City
country: United States
facility: MidAmerica Division, Inc., c/o Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: SSM Health Saint Louis University Hospital
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York-Presbyterian/Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai and The Mount Sinai Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals, The University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Cancer Institute Hematology- Charlotte
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute Hematology - Forsyth
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Health - LDS Hospital
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Franciscan Health
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Woden
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Monash University, Eastern Health-Box Hill Hospital
state: Victoria
city: Epping
country: Australia
facility: Northern Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Wien
country: Austria
facility: Wiener Gesundheitsverbund, Klinik Hietzing
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerp (ZNA) - Stuivenberg
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: University Hospital Gent
city: Haine-Saint-Paul
country: Belgium
facility: Hopital de Jolimont
city: Leuven
country: Belgium
facility: University Hospital Leuven (UZ Leuven) - Campus Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Halifax
country: Canada
facility: Queen Elizabeth II (QEII) Health Sciences Centre
city: Montreal
country: Canada
facility: Centre Integre Universitaire de Sante et de Services Sociaux(CIUSSS) de l'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - University Health Network
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
city: Jihormoravsky KRAJ
country: Czechia
facility: Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika FN Brno a LF MU
city: Olomouc
country: Czechia
facility: Fakultni nemocine Olomouc, Hemato-onkologicka klinika
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava, Klinika hematoonkologie
city: Prague
country: Czechia
facility: Fakulti nemocnice Kralovske Vinohrady, Internf hematologicka klinika FNKV a 3. LF UK
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Hematologicka ambulance
city: Amiens Cedex 1
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: CHU d'Angers
city: Bobigny
country: France
facility: Hopital Avicenne
city: Creteil
country: France
facility: Hopitaux Universitaires Henri Mondor
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
city: Le Chesnay Cedex
country: France
facility: Centre Hospitalier de Versailles
city: Lille Cedex
country: France
facility: Hôpital Claude Huriez (CHRU de Lillle)
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Nantes
country: France
facility: Centre Hospitalier Universitaire Nantes - Hotel Dieu
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud (CHLS)
city: Strasbourg
country: France
facility: Institut de Cancérologie Strasbourg Europe (ICANS)
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole
city: Vandoeuvre-les-Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin, Campus Virchow Klinikum, Medizinische Klinik mit Schwerpunkt Hamatologie, Onkologie und Tumorimmunologie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig GmbH Medizinische Klinik III/Hämatologie und Onkologie
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf, Klink fur Hamatologie, Onkologie und Klinische Immunologie
city: Düsseldorf
country: Germany
facility: Marien Hospital Dusseldorf GmbH, Klinik Fur Onkologie, Hamatologie Und Palliativmedizin
city: Flensburg
country: Germany
facility: Malteser Krankenhaus St. Franziskus Hospital,Med.Klinik I
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt Goethe Universitat Med. Klink II
city: Hamburg
country: Germany
facility: Asklepios Klink St.Georg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Hamatologie, Hamostaseologie, Onkologie und Stammzelltrandsplantation
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden Universitätsklinik fur Hämatologie, Onkologie, Hämostaseologie und Pastativrndezin, Universitatsklinik der Ruhr-Unive
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar Technischen Universitat Munchen
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg, Rahel-Straus-Straße 10
city: Regensburg
country: Germany
facility: Universitatsklinikum Regensburg, Klink fur Innere Medizin III
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Klinik fur Innere Medizin III
city: Hong Kong
country: Hong Kong
facility: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales 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: Tuen Mun Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
city: Gyor
country: Hungary
facility: Petz Aladár Egyetemi Oktató Kórház II. Belgyógyaszat - Haematológia
city: Hajdu-bihar
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Belgyogyaszati Klinika B epulet Hematologia
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Kozpont
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria delle Marche - SOD Clinica di Ematologia
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Monza
country: Italy
facility: ASST Monza-Ospedale San Gerardo
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Santa Maria della Misericordia
city: Pesaro
country: Italy
facility: Azienda Sanitaria Territoriale Pesaro e Urbino - "Stabilimento Ospedaliero San Salvatore - Muraglia" - U.O. Ematologia e Centro Trapianti
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul Saint Mary's Hospital
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medische Centra-Locatie Vrije Universiteit Medisch Centrum
city: Breda
country: Netherlands
facility: Amphia Hospital, department Oncologie, Route 43
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente - Enschede Koningsplein
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Maastricht
country: Netherlands
facility: Masstricht Universitair Medisch Centrum
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis, Nieuwegein
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Oslo
country: Norway
facility: Oslo University Hospital, Department of Hematology
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli, Oddzial Hematologiczny
city: Opole
country: Poland
facility: Szpital Wojewodozki w Opolu Sp. z 0.0. Oddzial Klinixzny Hematologii, Onkologii Hematologicznej i Chorob Wemnetrznych
city: Łódź
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M.Kopernika w Lodzi, Oddzial Hematologii Ogolnej
city: Alava
country: Spain
facility: Hospital Universitario Araba
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clinico
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Berne
country: Switzerland
facility: Inselspital Universitätsspital Bern
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Cheng Kung University Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
city: Warwick
country: United Kingdom
facility: South Warwickshire University NHS Foundation Trust
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: