Acute Myeloid Leukemia Clinical Trial

Study to Evaluate the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician’s Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Adults With TP53 Mutant Acute Myeloid Leukemia

Summary

The primary objective of this study is to compare the efficacy of magrolimab + azacitidine versus venetoclax + azacitidine in adults with previously untreated TP53 mutant acute myeloid leukemia (AML) who are appropriate for non-intensive therapy as measured by overall survival (OS).

View Eligibility Criteria

Eligibility Criteria

Key Inclusion Criteria:

Individuals with confirmation of AML by World Health Organization criteria, previously untreated for AML, and who have presence of at least 1 TP53 gene mutation that is not benign or likely benign based on evaluation by either central laboratory or an approved local laboratory (after central review of the bone marrow TP53 mitigation next-generation sequencing test results) (individuals with biallelic 17p deletions, loss of both 17p alleles, are eligible based on locally evaluated cytogenetics/karyotype/fluorescence in situ hybridization (FISH) report)
Individuals with white blood cell (WBC) count ≤ 20×10^3/microliter (μL) prior to randomization. If the individual's WBC is > 20×10^3/μL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be ≤ 20×10^3/μL prior to the first dose of study treatment and prior to each magrolimab dose the first 4 weeks (if the individual is randomized to the experimental arm) Note: Individuals can be treated with hydroxyurea and/or leukapheresis throughout the study or prior to randomization to reduce the WBC to ≤ 20×10^3/μL to enable eligibility for study drug dosing.
The hemoglobin must be ≥ 9 grams per deciliter (g/dL) prior to initial dose of study treatment Notes:Transfusions are allowed to meet hemoglobin eligibility
Individual has provided informed consent
Individual is willing and able to comply with clinic visits and procedure outlined in the study protocol
Individuals must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, except for individuals less than 75 years of age and appropriate for non-intensive treatment. For these individuals, the ECOG performance status score may be 0 to 3
Individuals must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 milliliters per minute calculated by the Cockcroft Gault formula
Adequate cardiac function as demonstrated by:
Lack of symptomatic congestive heart failure and clinically significant cardiac arrhythmias and ischemic heart disease
LVEF > 50% for individuals appropriate for intensive therapy
Adequate liver function as demonstrated by:
Aspartate aminotransferase ≤ 3.0 × upper limit of normal (ULN)
Alanine aminotransferase ≤ 3.0 × ULN
Total bilirubin ≤ 1.5 × ULN, or primary unconjugated bilirubin ≤ 3.0 × ULN if individual has a documented history of Gilbert's syndrome or genetic equivalent
Pretreatment blood cross-match completed
Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
Individuals must be willing to consent to mandatory pretreatment and ontreatment bone marrow biopsies (aspirate and trephines).

Key Exclusion Criteria:

Positive serum pregnancy test
Breastfeeding female
Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
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 (excluding hydroxyurea), hypomethylating agent (HMA), low dose cytarabine and/or venetoclax Note: Individuals with prior myelodysplastic syndrome (MDS) who have not received prior HMAs or chemotherapeutic agents for MDS are allowed on study. Other prior MDS therapies including, but not limited to, lenalidomide, erythroid stimulating agents, or similar RBC-direct therapies, are allowed. Localized non-central nervous system (CNS) radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer, hormonal therapy or maintenance for breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors are also not criteria for exclusion.
Individuals who are appropriate for intensive treatment but who have been previously treated with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones will be excluded.
Individuals receiving any live vaccine within 4 weeks prior to initiation of study treatments.
For individuals appropriate for intensive therapy, individuals treated with trastuzumab within 7 months prior to initiation of study treatments.
Current participation in another interventional clinical study
Known inherited or acquired bleeding disorders
Individuals appropriate for non-intensive therapy, who have received treatment with strong and/or moderate cytochrome P450 enzyme 3A (CYP3A) inducers within 7 days prior to the initiation of study treatments
Individuals appropriate for non-intensive therapy who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment
Individuals appropriate for non-intensive therapy who have malabsorption syndrome or other conditions that preclude enteral route of administration
Clinical suspicion of active CNS involvement with AML
Individuals who have acute promyelocytic leukemia
Significant disease or medical conditions, as assessed by the Investigator and Sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
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 anti-cancer therapies and have had no evidence of active malignancy for at least ≥ 1 year Note: Individuals on maintenance therapy alone who have no evidence of active malignancy for at least ≥ 1 year are eligible.
Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or human immunodeficiency virus (HIV) infection in medical history
Active HBV, and/or active HCV, and/or HIV following testing at screening:
Individuals who test positive for hepatitis B surface antigen (HBsAg). Individuals who test positive for hepatitis B core antibody (anti-HBc) will require HBV deoxyribose nucleic acid (DNA) by quantitative polymerase chain reaction (PCR) for confirmation of active disease
Individuals who test positive for HCV antibody. These individuals will require HCV ribose nucleic acid (RNA) quantitative PCR for confirmation of active disease
Individuals who test positive for HIV antibody
Individuals not currently receiving antiviral therapy and who have an undetectable viral load in the prior 3 months may be eligible for the study.

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

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

346

Study ID:

NCT04778397

Recruitment Status:

Recruiting

Sponsor:

Gilead Sciences

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 87 Locations for this study

See Locations Near You

University of Alabama at Birmingham
Birmingham Alabama, 35294, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte California, 91010, United States
USC/ Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States
UC Irvine Health
Orange California, 92868, United States
Colorado Blood Cancer Institute
Denver Colorado, 80218, United States
Miami Cancer Institute
Miami Florida, 33176, United States
AdventHealth Orlando
Orlando Florida, 32804, United States
Memorial Cancer Institute
Pembroke Pines Florida, 33028, United States
Winship Cancer Institute
Atlanta Georgia, 30322, United States
Northwestern Memorial Hospital/Main Lab
Chicago Illinois, 60611, United States
The University of Chicago Medical Centre
Chicago Illinois, 60637, United States
University of Kansas Hospital
Fairway Kansas, 66205, United States
Tulane Medical center
New Orleans Louisiana, 70112, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore Maryland, 21231, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
MidAmerica Division, Inc., c/o Research Medical Center
Kansas City Missouri, 64132, United States
Washington University School of Medicine - Siteman Cancer Center
Saint Louis Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Columbia University Medical Center - Herbert Irving Pavilion
New York New York, 10032, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill North Carolina, 27599, United States
The Ohio State University Wexner Medical Center/ James Cancer Hospital
Columbus Ohio, 43210, United States
University of Oklahoma Health Sciences Center - OU Health Stephenson Cancer Center
Oklahoma City Oklahoma, 73104, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
Philadelphia Pennsylvania, 19107, United States
St. Francis Cancer Center
Greenville South Carolina, 29607, United States
Prisma Health Cancer Institute
Greenville South Carolina, 29615, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
Froedtert Hospital / Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States
Canberra Hospital
Garran Australian Capital Territory, 2605, Australia
Calvary Master Newcastle
Waratah New South Wales, 2298, Australia
Westmead Hospital / Department of Haematology and Bone Marrow Transplantation
Westmead New South Wales, 2145, Australia
Princess Alexandra Hospital
Woolloongabba Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide South Australia, 5000, Australia
Andrew Love Cancer Centre, University Hospital Geelong
Geelong Victoria, 3220, Australia
The Alfred
Melbourne Victoria, 3004, Australia
Fiona Stanley Hospital
Murdoch Western Australia, 6150, Australia
Royal Perth Hospital
Perth Western Australia, 6000, Australia
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV
Brugge , 8000, Belgium
Universitair Ziekenhuis Brussel
Brussels , , Belgium
Universitaire Ziekenhuis Antwerpen
Edegem , , Belgium
Universitair Ziekenhuis Gent
Gent , 9000, Belgium
AZ Delta vzw
Roeselare , 8800, Belgium
Queen Elizabeth II Health Sciences Centre
Halifax , B3H 1, Canada
CHU d'Angers
Angers cedex , 49933, France
CHU de Caen
Caen cedex , 14033, France
Central Hospital Lyon Sud
Lyon , 69495, France
Institut Paoli Calmettes
Marseille , 13009, France
CHU de Nantes, Hotel Dieu
Nantes , 44093, France
CHU Nice - Hopital Archet 1
Nice , 6200, France
Gustave Roussy
Paris , 94805, France
IUCT Oncopole
Toulouse , 31059, France
Uniklinik RWTH Aachen, Medizinische Klunuk IV - Klinik fur Hamatologie, Onkologie, Hamastaseologie und Srammzelltransplantation
Aachen , 52074, Germany
Dept. of Hematology, Oncology and Tumor Immunology, Charite- University Medicine Berlin, Campus Virchow Klinikum
Berlin , 13353, Germany
Department of Hematology and Oncology, Braunschweig Community Hospital
Braunschweig , 38114, Germany
Universitatsklinikum Carl Gustav Carus Dresden an der Technische Universitat Dresden, Medizinische Klinik und Poliklinik 1, Bereich Hamatologie
Dresden , 01307, Germany
Dept. of Medicine II, University Hospital Hamburg-Eppendorf
Hamburg , 20246, Germany
Universitatsklinikum Heidelberg, Innere Medizin V, Hamatologie, Onkologie und Rheumatologie
Heidelberg , 69120, Germany
LMU - Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik III, Campus Grosshadern
München , 81377, Germany
Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Innere Medizin III
Ulm , 89081, Germany
Prince of Wales Hospital, The Chinese University of Hong Kong
Hong Kong , , Hong Kong
Queen Mary Hospital
Hong Kong , , Hong Kong
Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola-Malphigi U.O Ematologia
Bologna , 40138, Italy
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRS - Oncologia Medica
Meldola , 40174, Italy
SC Ematologia, Azienda Ospedaliera di Perugia - Santa Maria della Misericordia
Perugia , 06129, Italy
AORM - AO Riuniti Marche Norde - Pesaro Presidio "San Salvatore" - Muraglia
Pesaro , 61122, Italy
Fondazione PTV Policinico Tor Vergata
Roma , 00133, Italy
SCDU Ematologia e Terrapie cellulari AO O Ordine Mauriziano Torino
Torino , 10122, Italy
Fukushima Medical University Hospital
Fukushima-Shi , 960-1, Japan
Hospital of the University of Occupational and Environmental Health, Japan
Kitakyushu-shi , 807-8, Japan
Yamagata University Hospital
Yamagata , 990-9, Japan
Hospital del la Santa Creu i Sant Pau
Barcelona , 08025, Spain
Hospital Universitari Vall d'Hebron
Barcelona , 08035, Spain
Hospital Clinic de Barcelona
Barcelona , 08036, Spain
Institut Catala d'Oncologia
Barcelona , 08907, Spain
Hospital Universitario Reina Sofia
Cordoba , 14004, Spain
Hospital Regional Universitario de Malaga
Malaga , 29010, Spain
Complejo Asistencial Universitario de Salamanca - Hsopital Clinico
Salamanca , 37007, Spain
Hospital U. Marques de Valdecilla
Santander , 39008, Spain
Hospital Clinico Universitario de Valencia
Valencia , 46010, Spain
Hospital Universitari I Politècnic La Fe
Valencia , 46026, Spain
Universitetssjukhus, Hematologimottagnungen
Lund , 221 8, Sweden
Universitatsspital Basel - Klinik fur Hamatrologie, Bereich Innere Medizin
Basel , 4031, Switzerland
Inselspital, Universitatsspital Bern - Universitatsklinik fur Medizinisch Onkologie
Berne , CH 30, Switzerland
United Lincolnshire Hospitals NHS Trust, Pilgrim Hospital, Sibsey Road
Boston , PE21 , United Kingdom
Cambridge University Hospital NHS Foundation Trust
Cambridge , CB2 0, United Kingdom
Barts Health NHS Trust
City of London , EC1A , United Kingdom
NHS Tayside
Dundee , DD1 9, United Kingdom
University College London Hospitals NHS Foundation Trust
London , NW1 2, United Kingdom
Oxford University Hospital NHS Foundation Trust
Oxford , OX3 7, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton , SM2 5, United Kingdom
The Christie NHS Foundation Trust
Withington, Manchester , M20 4, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

346

Study ID:

NCT04778397

Recruitment Status:

Recruiting

Sponsor:


Gilead Sciences

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.