STATUS Terminated

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)

Gilead Clinical Study Information Center:
Monday – Friday, 5am – 6pm PT
Email: [email protected]

STATUS

Terminated

GILEAD STUDY ID

GS-US-546-5857

Gilead Clinical Study Information Center:
Monday – Friday, 5am – 6pm PT
Email: [email protected]

LAST UPDATED

February 05, 2025

Clinicaltrials.gov ID

EudraCT ID

CTSID

STUDY DOCUMENTS

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

Study details

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 red blood cell (RBC)-direct therapies, were 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

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)

For more information, please contact the

For more information, please contact the

OVERVIEW

PROTOCOL SUMMARY

Participation requirements

Study details

Eligibility information

Inclusion criteria

Exclusion criteria

Locations

Locations (156)

University of Alabama at Birmingham

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

USC/ Norris Comprehensive Cancer Center

Ronald Reagan UCLA Medical Center

UC Irvine Health

Colorado Blood Cancer Institute

Mayo Clinic Florida

Miami Cancer Institute

AdventHealth Orlando

Memorial Cancer Institute

Moffitt Cancer Center

Winship Cancer Institute

Northwestern Memorial Hospital/Main Lab

The University of Chicago Medical Centre

University of Kansas Hospital

University of Kentucky Medical Center

Tulane Medical center

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Massachusetts General Hospital

Dana-Farber Cancer Institute

Mayo Clinic Cancer Center Outpatient Pharmacy

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

SSM Health Saint Louis University Hospital

Roswell Park Cancer Institute

Columbia University Medical Center - Herbert Irving Pavilion

UNC Hospitals, The University of North Carolina at Chapel Hill

Duke Blood Cancer Center

The Ohio State University Wexner Medical Center/ James Cancer Hospital

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

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

St. Francis Cancer Center

Prisma Health Cancer Institute

Baylor College of Medicine Medical Center

The University of Texas MD Anderson Cancer Center

Huntsman Cancer Institute ,The University of Utah

Froedtert Hospital / Medical College of Wisconsin

Canberra Hospital

Calvary Master Newcastle

Westmead Hospital / Department of Haematology and Bone Marrow Transplantation

Princess Alexandra Hospital

Royal Adelaide Hospital

Andrew Love Cancer Centre, University Hospital Geelong

The Alfred

St Vincents Hospital Melbourne

Fiona Stanley Hospital

Royal Perth Hospital

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

Uniklinikum Salzburg, Universitatsklinik f. Innere Medizin III der PMU

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV

Universitair Ziekenhuis Brussel

Grand Hôpital De Charleroi - Notre Dame

Universitaire Ziekenhuis Antwerpen

Universitair Ziekenhuis Gent

AZ Delta vzw

Tom Baker Cancer Center

Queen Elizabeth II Health Sciences Centre

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

McGill University Health Centre

Sunnybrook Research Institute

Princess Margaret Cancer Centre

Aalborg University Hospital

Odense University Hospital

CHU d'Angers

CHU de Caen

CHRU Lille - Hospital Claude Huriez

CHU Limoges

Central Hospital Lyon Sud

Institut Paoli Calmettes