Study Details

OVERVIEW

A Phase 3, Randomized, Open-Label Study Evaluating 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 Patients With TP53 Mutant Acute Myeloid Leukemia (ENHANCE-2)

PROTOCOL SUMMARY

The goal of this clinical study is to compare the effectiveness of the study drugs, magrolimab in combination with azacitidine, versus venetoclax in combination with azacitidine in participants with previously untreated TP53 mutant acute myeloid leukemia (AML).

Participation Requirements

Age

18 Years +

Sex

All

Healthy Volunteers

Medical Condition

Acute Myeloid Leukemia

Gender

N/A

Date

July 2021 - March 2024

Study Type

Interventional

Study Phase

Phase 3

Product

Magrolimab, Venetoclax, Azacitidine, Cytarabine, Daunorubicin, Idarubicin, Steroidal Eye Drops

Eligibility Information

Inclusion Criteria

Individuals with confirmation of acute myeloid leukemia (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.
Left ventricular ejection fraction (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 on-treatment bone marrow biopsies (aspirate and trephines).

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.

Locations

Locations (156)

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States, 91010

USC/ Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States, 90095

UC Irvine Health

Orange, California, United States, 92868

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

Mayo Clinic Florida

Jacksonville, Florida, United States, 32224

Miami Cancer Institute

Miami, Florida, United States, 33176

AdventHealth Orlando

Orlando, Florida, United States, 32804

Memorial Cancer Institute

Pembroke Pines, Florida, United States, 33028

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Northwestern Memorial Hospital/Main Lab

Chicago, Illinois, United States, 60611

The University of Chicago Medical Centre

Chicago, Illinois, United States, 60637

University of Kansas Hospital

Fairway, Kansas, United States, 66205

University of Kentucky Medical Center

Lexington, Kentucky, United States, 40536

Tulane Medical center

New Orleans, Louisiana, United States, 70112

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Mayo Clinic Cancer Center Outpatient Pharmacy

Rochester, Minnesota, United States, 55905

MidAmerica Division, Inc., c/o Research Medical Center

Kansas City, Missouri, United States, 64132

SSM Health Saint Louis University Hospital

Saint Louis, Missouri, United States, 63110

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States, 10032

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Duke Blood Cancer Center

Durham, North Carolina, United States, 27705

The Ohio State University Wexner Medical Center/ James Cancer Hospital

Columbus, Ohio, United States, 43210

University of Oklahoma Health Sciences Center - OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

Philadelphia, Pennsylvania, United States, 19107

St. Francis Cancer Center

Greenville, South Carolina, United States, 29607

Prisma Health Cancer Institute

Greenville, South Carolina, United States, 29615

Baylor College of Medicine Medical Center

Houston, Texas, United States, 77030

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Huntsman Cancer Institute ,The University of Utah

Salt Lake City, Utah, United States, 84112

Froedtert Hospital / Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Canberra Hospital

Garran, Australian Capital Territory, Australia, 2605

Calvary Master Newcastle

Waratah, New South Wales, Australia, 2298

Westmead Hospital / Department of Haematology and Bone Marrow Transplantation

Westmead, New South Wales, Australia, 2145

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia, 4102

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Andrew Love Cancer Centre, University Hospital Geelong

Geelong, Victoria, Australia, 3220

The Alfred

Melbourne, Victoria, Australia, 3004

St Vincents Hospital Melbourne

Melbourne, Victoria, Australia, 3122

Fiona Stanley Hospital

Murdoch, Western Australia, Australia, 6150

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

Univ. -Klinik für Hämatologie und Internistische Onkologie, Kepler Universitätskilkun GmbHMed

Linz, Austria, 4021

Uniklinikum Salzburg, Universitatsklinik f. Innere Medizin III der PMU

Salzburg, Austria, 5020

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV

Brugge, Belgium, 8000

Universitair Ziekenhuis Brussel

Brussels, Belgium

Grand Hôpital De Charleroi - Notre Dame

Charleroi, Belgium, 6000

Universitaire Ziekenhuis Antwerpen

Edegem, Belgium

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

AZ Delta vzw

Roeselare, Belgium, 8800

Tom Baker Cancer Center

Calgary, Canada, T2N 4N2

Queen Elizabeth II Health Sciences Centre

Halifax, Canada, B3H 1V7

CIUSSS de L'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont

Montreal, Canada, H1T 2M4

McGill University Health Centre

Montreal, Canada, H4A 3J1

Sunnybrook Research Institute

Toronto, Canada, M4N 3M5

Princess Margaret Cancer Centre

Toronto, Canada, M5G 2M9

Aalborg University Hospital

Aalborg, Denmark, 9000

Odense University Hospital

Odense C, Denmark, 5000

CHU d'Angers

Angers cedex, France, 49933

CHU de Caen

Caen cedex, France, 14033

CHRU Lille - Hospital Claude Huriez

Lille, France, 59037

CHU Limoges

Limoges, France, 87042

Central Hospital Lyon Sud

Lyon, France, 69495

Institut Paoli Calmettes

Marseille, France, 13009

CHU de Nantes, Hotel Dieu

Nantes, France, 44093

CHU Nice - Hopital Archet 1

Nice, France, 6200

Gustave Roussy

Paris, France, 94805

Hopital Haut-Leveque

Pessac, France, 33604

IUCT Oncopole

Toulouse, France, 31059

Hopitaux de Brabois

Vandoeuvre-lès-Nancy, France

Uniklinik RWTH Aachen, Medizinische Klunuk IV - Klinik fur Hamatologie, Onkologie, Hamastaseologie und Srammzelltransplantation

Aachen, Germany, 52074

Dept. of Hematology, Oncology and Tumor Immunology, Charite- University Medicine Berlin, Campus Virchow Klinikum

Berlin, Germany, 13353

Department of Hematology and Oncology, Braunschweig Community Hospital

Braunschweig, Germany, 38114

Universitatsklinikum Carl Gustav Carus Dresden an der Technische Universitat Dresden, Medizinische Klinik und Poliklinik 1, Bereich Hamatologie

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf -Klinik für Hämatologie, Onkologie und Klinische Immunologie

Dusseldorf, Germany, 40225

Dept. of Medicine II, University Hospital Hamburg-Eppendorf

Hamburg, Germany, 20246

Universitatsklinikum Heidelberg, Innere Medizin V, Hamatologie, Onkologie und Rheumatologie

Heidelberg, Germany, 69120

Universitatsklinikum Schleswig-Holstein

Kiel, Germany, 24105

Universitatsklinikum Koln

Köln, Germany, 50937

Klinikum Ludwigshafen Medizinische Klinik A

Ludwigshafen, Germany, 67063

Klinikum rechts der Isar der Technischen Universitat Munchen, Klinik und Poliklinik fur Innere Medizin III

Muenchen, Germany, 81675

LMU - Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik III, Campus Grosshadern

München, Germany, 81377

Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Innere Medizin III

Ulm, Germany, 89081

Prince of Wales Hospital, The Chinese University of Hong Kong

Hong Kong, Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong

Azienda Ospedaliero Universitaria delle Marche

Ancona, Italy, I-60126

AOU Consorziale Policlinico Bari

Bari, Italy, 70124

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola-Malphigi U.O Ematologia

Bologna, Italy, 40138

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRS - Oncologia Medica

Meldola, Italy, 40174

Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli U.O.S.C. di Ematologia con Trapianto di Midollo Osseo

Napoli, Italy, 80131

SC Ematologia, Azienda Ospedaliera di Perugia - Santa Maria della Misericordia

Perugia, Italy, 06129

AORM - AO Riuniti Marche Norde - Pesaro Presidio "San Salvatore" - Muraglia

Pesaro, Italy, 61122

Fondazione PTV Policinico Tor Vergata

Roma, Italy, 00133

SCDU Ematologia e Terrapie cellulari AO O Ordine Mauriziano Torino

Torino, Italy, 10122

ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi

Varese, Italy, 21100

Hyogo Prefectural Amagasaki General Medical Center

Amagasaki, Japan, 660-8550

Chiba Aoba Municipal Hospital

Chiba, Japan, 260-0852

University of Yamanashi Hospital

Chuo-City, Japan, 409-3898

Kyushu University Hospital

Fukuoka, Japan, 812-8582

Fukushima Medical University Hospital

Fukushima-Shi, Japan, 960-1295

Aiiku Hospital

Hokkaido, Japan, 064-0804

Tokai University School of Medicine

Isehara, Japan, 259-1193

Kanazawa University Hospital

Kanazawa, Japan, 920-8641

National Cancer Center Hospital East

Kashiwa, Japan, 277-8577

Hospital of the University of Occupational and Environmental Health, Japan

Kitakyushu-shi, Japan, 807-8555

Kobe City Medical Center General Hospital

Kobe-city, Japan, 650-0047

Gunmaken Saiseikai Maebashi Hospital

Maebashi, Japan, 371-0821

Ehime Prefectural Center Hospital

Matsuyama, Japan, 790-0024

Nagasaki University Hospital

Nagasaki, Japan, 852-8501

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya-Shi, Japan, 466-8650

Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

Nagoya, Japan, 453-8511

Okayama University Hospital

Okayama-Shi, Japan, 700-8558

Osaka Metropolitan University Hospital

Osaka-Shi, Japan, 545-8586

Kindai University Hospital

Osakasayama, Japan, 589-8511

National University Corporation Tohoku University Tohoku University Hospital

Sendai, Japan, 980-8574

NTT Medical Center Tokyo

Shinagawa-Ku, Japan, 141-8625

Yamagata University Hospital

Yamagata, Japan, 990-9585

University of Fukui Hospital

Yoshida-gun, Japan, 910-1193

Hospital General Universitario de Alicante

Alicante, Spain, 3010

Hospital del la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Institut Catala d'Oncologia

Barcelona, Spain, 08907

Complejo Asistencial Universitario de Burgos/H.U. de Burgos

Burgos, Spain, 09006

Hospital Universitario Reina Sofia

Cordoba, Spain, 14004

Complejo Hospitalario San Pedro de Alcantara

Cáceres, Spain, 10001

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, Spain, 35010

Hospital Universitario de La Princesa

Madrid, Spain, 28006

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28007

MD Anderson Cancer Center Madrid

Madrid, Spain, 28033

Hospital Regional Universitario de Malaga

Malaga, Spain, 29010

Hospital Universitario Central de Asturias

Oviedo, Spain, 33011

Clinica Universidad de Navarra - Pamplona (Main Site)

Pamplona, Spain, 31008

Complejo Asistencial Universitario de Salamanca - Hsopital Clinico

Salamanca, Spain, 37007

Hospital U. Marques de Valdecilla

Santander, Spain, 39008

Hospital Clinico Universitario de Valencia

Valencia, Spain, 46010

Hospital Universitari I Politècnic La Fe

Valencia, Spain, 46026

Universitetssjukhus, Hematologimottagnungen

Lund, Sweden, 221 85

Universitatsspital Basel - Klinik fur Hamatrologie, Bereich Innere Medizin

Basel, Switzerland, 4031

Inselspital, Universitatsspital Bern - Universitatsklinik fur Medizinisch Onkologie

Berne, Switzerland, CH 3010

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B15 2GW

United Lincolnshire Hospitals NHS Trust, Pilgrim Hospital, Sibsey Road

Boston, United Kingdom, PE21 9QS

Cambridge University Hospital NHS Foundation Trust

Cambridge, United Kingdom, CB2 0QQ

Cardiff and Vale University Health Board

Cardiff Wales, United Kingdom, CF14 4XW

Barts Health NHS Trust

City of London, United Kingdom, EC1A 7BE

NHS Tayside

Dundee, United Kingdom, DD1 9SY

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

University College London Hospitals NHS Foundation Trust

London, United Kingdom, NW1 2PG

King's College NHS Foundation Trust

London, United Kingdom, SE5 9RS

Oxford University Hospital NHS Foundation Trust

Oxford, United Kingdom, OX3 7LE

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom, SM2 5PT

The Christie NHS Foundation Trust

Withington, United Kingdom, M20 4BX

Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated (ENHANCE-2)