Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

— ENHANCE-3  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05079230
• Other study ID #: GS-US-590-6154
• Secondary ID: 2021-003434-36MO
• Status: Terminated
• Phase: Phase 3
• Start date: July 7, 2022
• Est. completion date: April 11, 2024

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 378
• Est. completion date: April 11, 2024
• Est. primary completion date: April 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (SIRPa)-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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Magrolimab
Administered intravenously (IV)
• Venetoclax
Tablets administered orally
• Azacitidine
Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)
• Magrolimab Placebo
Administered intravenously (IV)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is measured from the date of randomization to the date of death from any cause.	Randomization up to death or end of study (up to 5 years) whichever occurs first
Secondary	Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)	The CR + CRh rate is the proportion of participants who achieve a CR (including CRMRD- and complete remission with positive or unknown minimal residual disease (CRMRD+/unk)) or CRh as defined by CR with partial platelet and absolute neutrophil count recovery within 6 cycles of treatment while on study prior to initiation of any new anti-acute myeloid leukemia (AML) therapy or stem cell transplant (SCT).	Up to 7 months
Secondary	Rate of Complete Remission (CR)	CR is defined as the proportion of the participants who achieve CR within 6 cycles of treatment as determined by the investigator while on study prior to initiation of any new anti-acute myeloid leukemia (AML) therapy or stem cell transplant (SCT)	Up to 7 months
Secondary	Event-Free Survival (EFS)	EFS is defined as time from the date of randomization to the earliest date of the documented relapse from CR, treatment failure (defined as failure to achieve CR within 6 cycles of treatment), or death from any cause.	Randomization up to end of study (up to 5 years)
Secondary	Duration of CR + CRh in Participants who achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)	The duration of CR + CRh is measured from the time the assessment criteria are first met for CR (including CRMRD- and CRMRD+/unk) or CRh within 6 cycles of treatment until the first date of AML relapse or death (including assessments post SCT).	Up to 5 years
Secondary	Duration of Complete Remission (DCR) in Participants who achieved Complete Remission (CR)	The DCR is measured from the time the assessment criteria are first met for CR (including CRMRD- and CRMRD+/unk) within 6 cycles of treatment until the first date of AML relapse or death (including assessments post SCT).	Up to 5 years
Secondary	Rate of CR/Complete Remission With Partial Hematologic Recovery Without Minimal Residual Disease (CRhMRD-)	The CR/CRhMRD- rate is the proportion of participants who achieve a CRMRD- or CRhMRD- within 6 cycles of treatment while on study prior to initiation of any new anti-AML therapy or SCT.	Up to 5 years
Secondary	Rate of Complete Remission Without Minimal Residual Disease (CRMRD-)	The CRMRD- rate is the proportion of participants who achieve a CRMRD- within 6 cycles of treatment.	Up to 5 years
Secondary	Transfusion Independence Conversion Rate	The transfusion independence conversion rate includes both red blood cell (RBC) transfusion independence rate and platelet transfusion independence rate. The RBC transfusion independence conversion rate is the proportion of participants who have a 56-day or longer period with no RBC or whole blood transfusions at any time between the date of first dose of study treatment and discontinuation of study treatment among all participants who are RBC transfusion dependent at baseline. The platelet transfusion independence conversion rate is the proportion of participants who have a 56-day or longer period with no platelet transfusions at any time between the date of first dose of study treatment and discontinuation of study treatment among all participants who are platelet transfusion dependent at baseline.	First dose date up to End of Treatment (EOT) (up to 5 years)
Secondary	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	The TTD on the EORTC QLQ-C30 GHS/QoL scale is defined as time from the date of randomization to the time a patient experienced at least 1 threshold value deterioration from baseline or death, whichever is earlier. Questionnaire includes 30 questions resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 1 GHS/QoL scale, 3 symptom scales (fatigue, nausea and vomiting, pain), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). After linear transformation, all scales and single item measures range in score from 0-100. Higher score on GHS/QoL scale means better GHS/QoL.	Randomization up to end of study (up to 5 years)
Secondary	TTD on the EORTC QLQ-C30 Physical Functioning Scale	The TTD on the EORTC QLQ-C30 physical functioning scale is defined as time from the date of randomization to the time a patient experienced at least 1 threshold value deterioration from baseline or death, whichever is earlier. Physical functioning scale is one of the five functional scales of the EORTC QLQ-; C30 questionnaire. After linear transformation, scale range in score from 0-100. A higher score on functional scales means better functioning and better quality of life.	Randomization up to end of study (up to 5 years)
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)		First dose date up to last dose date (up to 5 years) plus 70 days
Secondary	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities		First dose date up to last dose date (up to 5 years) plus 70 days
Secondary	Serum Concentration of Magrolimab over time		First dose date up to EOT (up to 5 years)
Secondary	Rate of Anti-Magrolimab Antibody Incidence	Rate of anti-magrolimab antibody incidence is defined as the percentage of participants with anti-magrolimab antibodies.	First dose date up to EOT (up to 5 years)
Secondary	Magnitude of Anti-Magrolimab Antibody Incidence		First dose date up to EOT (up to 5 years)

External Links

•   Gilead Clinical Trials Website