Acute Myeloid Leukemia Clinical Trial
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
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).
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.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 147 Locations for this study
Birmingham Alabama, 35294, United States
Duarte California, 91010, United States
Los Angeles California, 90033, United States
Los Angeles California, 90095, United States
Orange California, 92868, United States
Denver Colorado, 80218, United States
Jacksonville Florida, 32224, United States
Miami Florida, 33176, United States
Orlando Florida, 32804, United States
Pembroke Pines Florida, 33028, United States
Tampa Florida, 33612, United States
Atlanta Georgia, 30322, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60637, United States
Fairway Kansas, 66205, United States
Lexington Kentucky, 40536, United States
New Orleans Louisiana, 70112, United States
Baltimore Maryland, 21231, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Rochester Minnesota, 55905, United States
Kansas City Missouri, 64132, United States
Saint Louis Missouri, 63110, United States
Buffalo New York, 14263, United States
New York New York, 10032, United States
Chapel Hill North Carolina, 27599, United States
Durham North Carolina, 27705, United States
Columbus Ohio, 43210, United States
Oklahoma City Oklahoma, 73104, United States
Philadelphia Pennsylvania, 19107, United States
Greenville South Carolina, 29607, United States
Greenville South Carolina, 29615, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Salt Lake City Utah, 84112, United States
Milwaukee Wisconsin, 53226, United States
Garran Australian Capital Territory, 2605, Australia
Waratah New South Wales, 2298, Australia
Westmead New South Wales, 2145, Australia
Woolloongabba Queensland, 4102, Australia
Adelaide South Australia, 5000, Australia
Geelong Victoria, 3220, Australia
Melbourne Victoria, 3004, Australia
Melbourne Victoria, 3122, Australia
Murdoch Western Australia, 6150, Australia
Perth Western Australia, 6000, Australia
Linz , 4021, Austria
Salzburg , 5020, Austria
Brugge , 8000, Belgium
Brussels , , Belgium
Charleroi , 6000, Belgium
Edegem , , Belgium
Gent , 9000, Belgium
Roeselare , 8800, Belgium
Calgary , T2N 4, Canada
Halifax , B3H 1, Canada
Montreal , H1T 2, Canada
Montreal , H4A 3, Canada
Toronto , M4N 3, Canada
Toronto , M5G 2, Canada
Aalborg , 9000, Denmark
Odense C , 5000, Denmark
Angers cedex , 49933, France
Caen cedex , 14033, France
Lille , 59037, France
Limoges , 87042, France
Lyon , 69495, France
Marseille , 13009, France
Nantes , 44093, France
Nice , 6200, France
Paris , 94805, France
Pessac , 33604, France
Toulouse , 31059, France
Vandoeuvre-lès-Nancy , , France
Aachen , 52074, Germany
Berlin , 13353, Germany
Braunschweig , 38114, Germany
Dresden , 01307, Germany
Dusseldorf , 40225, Germany
Hamburg , 20246, Germany
Heidelberg , 69120, Germany
Kiel , 24105, Germany
Köln , 50937, Germany
Ludwigshafen , 67063, Germany
Muenchen , 81675, Germany
München , 81377, Germany
Ulm , 89081, Germany
Hong Kong , , Hong Kong
Hong Kong , , Hong Kong
Ancona , I-601, Italy
Bari , 70124, Italy
Bologna , 40138, Italy
Meldola , 40174, Italy
Napoli , 80131, Italy
Perugia , 06129, Italy
Pesaro , 61122, Italy
Roma , 00133, Italy
Torino , 10122, Italy
Varese , 21100, Italy
Amagasaki , 660-8, Japan
Chiba , 260-0, Japan
Chuo-City , 409-3, Japan
Fukuoka , 812-8, Japan
Fukushima-Shi , 960-1, Japan
Hokkaido , 064-0, Japan
Isehara , 259-1, Japan
Kanazawa , 920-8, Japan
Kashiwa , 277-8, Japan
Kitakyushu-shi , 807-8, Japan
Kobe-city , 650-0, Japan
Maebashi , 371-0, Japan
Matsuyama , 790-0, Japan
Nagasaki , 852-8, Japan
Nagoya-Shi , 466-8, Japan
Nagoya , 453-8, Japan
Okayama-Shi , 700-8, Japan
Osaka-Shi , 545-8, Japan
Osakasayama , 589-8, Japan
Sendai , 980-8, Japan
Shinagawa-Ku , 141-8, Japan
Yamagata , 990-9, Japan
Yoshida-gun , 910-1, Japan
Alicante , 3010, Spain
Barcelona , 08025, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Barcelona , 08907, Spain
Burgos , 09006, Spain
Cordoba , 14004, Spain
Cáceres , 10001, Spain
Las Palmas de Gran Canaria , 35010, Spain
Madrid , 28006, Spain
Madrid , 28007, Spain
Madrid , 28033, Spain
Malaga , 29010, Spain
Oviedo , 33011, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
Santander , 39008, Spain
Valencia , 46010, Spain
Valencia , 46026, Spain
Lund , 221 8, Sweden
Basel , 4031, Switzerland
Berne , CH 30, Switzerland
Birmingham , B15 2, United Kingdom
Boston , PE21 , United Kingdom
Cambridge , CB2 0, United Kingdom
Cardiff Wales , CF14 , United Kingdom
City of London , EC1A , United Kingdom
Dundee , DD1 9, United Kingdom
Glasgow , G12 0, United Kingdom
London , NW1 2, United Kingdom
London , SE5 9, United Kingdom
Oxford , OX3 7, United Kingdom
Sutton , SM2 5, United Kingdom
Withington , M20 4, United Kingdom
How clear is this clinincal trial information?