Acute Myeloid Leukemia MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Magrolimab
Product Code: GS-4721
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Magrolimab
Current Sponsor code: GS-4721
Concentration unit: mg/ml millig
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Patients with confirmation of AML by World Health Organization criteria, previously untreated for AML, and who have presence of: a) 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 mutation next-generation sequencing test results) b) Biallelic 17p deletions, loss of both 17p alleles, based on locally evaluated cytogenetics/karyotype/fluorescence in situ hybridization (FISH) report. 2)Patients with white blood cell (WBC) count = 20 x 10^3/µL prior to randomization. If the patient’s WBC is > 20 x 10^3/µL prior to randomization, the patient 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 dose for the first 4 weeks (if the patient is randomized to the experimental arm). NOTE: Patients can be treated with hydroxyurea and/or leukapheresis throughout the study or prior to randomization to reduce the WBC to = 20 x 10^3/µL to enable eligibility for study drug dosing. 3)The hemoglobin must be = 9g/dL prior to initial dose of study treatment. NOTE: Transfusions are allowed to meet hemoglobin eligibility. 4)Patient has provided informed consent. 5)Patient is willing and able to comply with clinic visits and procedure outlined in the study protocol. 6)Male or female, = 18 years of age 7)Patients must have an ECOG performance status of 0 to 2, except for patients less than 75 years of age and appropriate for non-intensive treatment. For these patients, the ECOG performance status score may be 0 to 3. 8)Patients must have adequate renal function as demonstrated by a creatinine clearance = 30 mL/min; calculated by the Cockcroft Gault formula 9)Adequate cardiac function as demonstrated by: a) Lack of symptomatic congestive heart failure and clinically significant cardiac arrhythmias and ischemic heart disease. b) LVEF > 50% for patients appropriate for intensive therapy. 10)Adequate liver function as demonstrated by: a) Aspartate aminotransferase = 3.0 x ULN b) Alanine aminotransferase = 3.0 x ULN c) Total bilirubin = 1.5 x ULN, or primary unconjugated bilirubin = 3.0 x ULN if patient has a documented history of Gilbert’s syndrome or genetic equivalent. 11)Pretreatment blood cross-match completed. 12)Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. 13)Patients must be willing to consent to mandatory pretreatment and on treatment bone marrow biopsies (aspirate and trephines). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 104 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 242
Exclusion criteria
Exclusion criteria: 1)Subjects that are unable to give consent. To give consent, the individual concerned must be of legal age and be able to understand the nature, significance and implications of the clinical study and form their rational intentions in light of these. 2)Positive serum pregnancy test 3)Breastfeeding female 4)Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient 5)Prior treatment with any of the following: a)CD47 or signal regulatory protein alpha (SIRPa)-targeting agents b)Antileukemic therapy for the treatment of AML eg hypomethylating agent [HMA], low dose cytarabine and/or venetoclax, excluding hydroxyurea. NOTE: Patients 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. c) Patients 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. 6)Patients receiving any live vaccine within 4 weeks prior to initiation of study treatments. 7) For patients appropriate for intensive therapy, patients treated with trastuzumab within 7 months prior to initiation of study treatments. 8)Current participation in another interventional clinical study. 9)Known inherited or acquired bleeding disorders. 10)Patients appropriate for non-intensive therapy, who have received treatment with strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatments. 11)Patients 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. 12)Patients appropriate for non-intensive therapy who have malabsorption syndrome or other conditions that preclude enteral route of administration. 13)Clinical suspicion of active CNS involvement with AML. 14)Patients who have acute promyelocytic leukemia. 15)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. 16)Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anti-cancer therapies and have had no evidence of active malignancy for at least = 1 year. NOTE: Patients on maintenance therapy alone who have no evidence of active malignancy for at least = 1 year are eligible. 17)Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or HIV infection in medical history. 18
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of magrolimab + azacitidine versus venetoclax + azacitidine in patients with previously untreated TP53 mutant acute myeloid leukemia (AML) who are appropriate for non intensive therapy as measured by overall survival (OS).;Secondary Objective: The secondary objectives of this study are as follows: •To compare the efficacy of magrolimab + azacitidine versus physician’s choice of venetoclax + azacitidine or 7 + 3 chemotherapy in all patients with previously untreated TP53 mutant AML as measured by OS. •To compare the efficacy of magrolimab + azacitidine versus physician’s choice of venetoclax + azacitidine or 7 + 3 chemotherapy in all patients as measured by event-free survival (EFS). •To compare the efficacy of magrolimab + azacitidine versus physician’s choice of venetoclax + azacitidine or 7 + 3 chemotherapy in all patients as measured by conversion rate of transfusion dependence to transfusion independence. See protocol for extensive list.;Primary end point(s): Overall Survival in the Stratum of Patients Appropriate for Non-intensive Therapy;Timepoint(s) of evaluation of this end point: Date of randomization to the date of death from any cause. Those whose deaths are not observed during the study will be censored at their last known alive date. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (1)Overall Survival in All Patients (2)Event-Free Survival in All Patients (3)Transfusion Independence Conversion Rate in All Patients (4)Rate of Complete Remission within 6 Months in All Patients (2 months for patients receiving 7 + 3 chemotherapy) (5)Rate of CR without Minimal Residual Disease within 6 Months in All Patients (2 months for patients receiving 7 + 3 chemotherapy) (6)Time until Meaningful Definitive Deterioration (TUDD) on the EORTC QLQ-C30 GHS/QoL Scale in All Patients and TUDD on the EORTC QLQ-C30 Physical Functioning Scale in All Patients (7)Rate of CR + CRh within 6 Months in All Patients (2 months for patients receiving 7 + 3 chemotherapy) (8)Duration of Complete Remission (9)Duration of CR + CRh (10)Incidence of Grade = 3 treatment-emergent adverse events and Incidence of Grade = 3 treatment-emergent laboratory abnormalities (11)Serum concentration of magrolimab and Rate of anti-magrolimab antibody incidence;Timepoint(s) of evaluation of this end point: (1)The OS is measured from the date of randomization to the date of death from any cause. (2)The EFS is defined as time from the date of randomization to the earliest date of documented relapse from CR, treatment failure (defined as failure to achieve CR within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or up to 2 months of treatment with 7 + 3 chemotherapy), or death from any cause. Please see protocol for extensive list. | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hong Kong, Israel, Italy, Japan, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed