Myeloid MalignanciesPhase 2NCT04778410
Study of Magrolimab Combinations in Participants With Myeloid Malignancies
A Phase 2 study testing Magrolimab, Azacitidine and Venetoclax in people with Myeloid Malignancies, run by Gilead Sciences at 21 sites in 3 countries.
Trial summary
The goal of this clinical study is to learn more about the safety and dosing of the study drug, magrolimab (Mag), in combination with anti-leukemia therapies in participants with acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloid Malignancies
- What is being tested?
- Magrolimab, Azacitidine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 28 Jun 2021to 4 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Individuals:
- White blood cell (WBC) count ≤ 20 × 10^3/microliter (μL) prior to first dose of study treatment. If the individual's WBC count is > 20 × 10^3/ μL prior to first dose of study treatment, the individual can be enrolled, assuming all other eligibility criteria are met
- For individuals with prior cardiac history, the hemoglobin must be ≥ 9 grams per deciliter (g/dL) prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility
- Adequate liver function
- Adequate renal function
- Individual has provided informed consent
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- Individual is willing and able to comply with clinic visits and procedures outlined in the study protocol
- 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 (trephines), unless not feasible as determined by the investigator and discussed with the sponsor
- Safety Run-in Cohort 1 and Phase 2 Cohort 1 (Ineligible (1L) Unfit acute myeloid leukemia (AML) Magrolimab + Venetoclax + Azacitidine):
- Newly diagnosed, previously untreated individuals with histological confirmation of AML by world health organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, comorbidity, or other factors. Individuals must be considered ineligible for induction therapy defined by the following:
- ≥ 75 years of age
- ≥ 18 to 74 years of age with at least 1 of the following comorbidities:
- Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
- Left ventricular ejection fraction (LVEF) ≤ 50%
- Creatinine clearance (CrCl) < 45 mL/min calculated by the Cockcroft-Gault formula or measured by 24 hours' urine collection
- Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy that must be approved by the sponsor medical monitor before study enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
- Individuals who have not received prior anti-leukemia therapy for AML (excluding hydroxyurea or oral etoposide), hypomethylating agent (HMA), low-dose cytarabine, and/or venetoclax. Individuals with prior myelodysplastic syndrome (MDS) cannot have received a prior HMA, venetoclax, or a chemotherapeutic agent. Other prior MDS therapies, including but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell (RBC) -direct therapies, are allowed
- Individuals who have not received strong and/or moderate cytochrome P450 enzyme (CYP) 3A inducers (such as St. John's Wort) within 7 days prior to the initiation of study treatment
- Individuals who have not consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment or are willing to discontinue consumption of these while receiving study drug
- Individuals without malabsorption syndrome or other conditions that preclude enteral route of administration
- Safety Run-in Cohort 2 and Phase 2 Cohort 2 (Relapsed/refractory (R/R) AML Magrolimab+Mitoxantrone + Etoposide + Cytarabine (MEC)):
- Individuals with confirmation of AML by WHO criteria who are refractory to or have experienced first relapse after initial intensive chemotherapy. Note: Individuals who are relapsed after or are refractory to more than 1 line of anti-AML treatment are not eligible. Individuals who relapsed after undergoing stem cell transplant may be eligible.
- At least 2 weeks must have elapsed since any prior anti-leukemia agents. Note: Localized non-central nervous system (CNS) radiotherapy, hydroxyurea, and erythroid and/or myeloid growth factors are not criteria for exclusion
- ECOG performance status of 0 to 2
- Individuals with LVEF > 50%, lack of symptomatic congestive heart failure, or clinically significant cardiac arrhythmias
- Must not have been treated with trastuzumab within 7 months prior to the initiation of study treatment
- Individuals who have not previously received maximum cumulative doses of anthracyclines and anthracenediones
- Individuals without degenerative or toxic encephalopathies.
- Individuals who did not undergo hematopoietic SCT in the past 100 days, are not on immunosuppressive therapy post SCT in the 2 weeks prior to the first dose of study treatment, or have no active clinically significant graft-versus-host disease.
- Safety Run-in Cohort 3 and Phase 2 Cohort 3 (Post-chemo Maintenance Magrolimab+CC-486):
- Individuals with histological confirmation of AML by WHO criteria who achieved a complete remission (CR) or CR with incomplete hematologic recovery (CRi) with presence of MRD (MRD positive by flow cytometry assay, defined as ≥ 0.1% detectable MRD) after intensive induction chemotherapy with or without consolidation therapy, prior to starting maintenance therapy for newly diagnosed AML, and who are not candidates for hematopoietic stem cell transplantation (SCT) within 1 year of achievement of initial remission
- ECOG performance status of 0 to 2
- Individuals without malabsorption syndrome or other conditions that preclude enteral route of administration
Who cannot join
- Positive serum pregnancy test
- Breastfeeding female
- Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
- Individuals receiving any live virus vaccine within 4 weeks prior to initiation of study treatments
- Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) -targeting agents
- Current participation in another interventional clinical trial
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- Known inherited or acquired bleeding disorders
- Clinical suspicion of or documented 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 over 1 year. Previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion
- 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 or C infection or human immunodeficiency virus
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States17 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Roswell Park Cancer Institute
Buffalo, New York, 14263
Levine Cancer Institute
Charlotte, North Carolina, 28204
The University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75246
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
OU Health, Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Stanford Cancer Center
Palo Alto, California, 94305
Swedish Cancer Institute
Seattle, Washington, 98104
Washington University School of Medicine
St Louis, Missouri, 63110
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
The Alfred Hospital
Melbourne, Victoria, 3004
Royal Perth Hospital
Perth, Western Australia, 6000
United Kingdom1 site
Oxford University Hospitals NHS Foundation Trust, Churchill Hospital
Oxford, OX3 9DU
About this study
Official title: A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Myeloid Malignancies
The goal of this clinical study is to learn more about the safety and dosing of the study drug, magrolimab (Mag), in combination with anti-leukemia therapies in participants with acute myeloid leukemia (AML).
Read the detailed description
The anti-leukemia therapies are defined as follows:
- Venetoclax (Ven)
- Azacitidine (Aza)
- Mitoxantrone, etoposide, and cytarabine (MEC)
This study consists of 3 safety run-in cohorts;
- Safety Run-in Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Safety Run-in Cohort 2 (R/R AML Mag + MEC)
- Safety Run-in Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Participants will receive treatment at the assigned dose level for at least 4 cycles in the Safety Run-in cohorts, after which they may continue at the assigned dose level or switch to the RP2D upon agreement between the investigator and the sponsor. After completion of each safety run-in cohort and identification of the RP2D for that cohort, participants may be enrolled into the corresponding Phase 2 cohorts;
- Phase 2 Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Phase 2 Cohort 2 (R/R AML Mag + MEC)
- Phase 2 Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Cycle length is 28 days for both the Safety Run-in and Phase 2 cohorts.
Note: All cohorts are closed to screening and enrollment.
- Conditions
- Myeloid Malignancies
- Being tested
- Magrolimab, Azacitidine, Venetoclax, Mitoxantrone, Etoposide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagrolimabDrug
Also called GS-4721
Administered intravenously
AzacitidineDrug
Administered either subcutaneously or IV, 75 mg/milligram per square (m^2) on Days 1 to 7 or Days 1 to 5, 8 and 9 during every cycle
VenetoclaxDrug
Administered orally at a dose of 100 mg on Day 1, 200 mg on Day 2, 400 mg on Days 3-28 during Cycle 1, followed by 400 mg on Days 1-28 during every cycle
MitoxantroneDrug
Administered intravenously, 8 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3
EtoposideDrug
Administered intravenously, 100 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3
CytarabineDrug
Administered intravenously, 1000 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3
CC-486Drug
Also called Onureg
Administered orally, 300 mg on Days 1-14 during each cycle
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine | Experimental | Participants with newly diagnosed untreated acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then every week (QW) x 5 doses; 30 mg/kg every 2 weeks (Q2W) beginning 1 week after the 5 weekly 30 mg/kg dose in every 28-day cycle along with azacitidine and venetoclax first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. Receives: Drug: Magrolimab; Drug: Azacitidine; Drug: Venetoclax |
| Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine | Experimental | Participants with relapsed/refractory (RR) AML after intensive induction chemotherapy will receive magrolimab 1 mg/ on Days 1, 4; 15 mg/kg, on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with mitoxantrone + etoposide + cytarabine (MEC) first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. Receives: Drug: Magrolimab; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine |
| Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486 | Experimental | Participants with AML who achieved CR or CRi with MRD positivity following intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with CC-486 as maintenance therapy first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. Receives: Drug: Magrolimab; Drug: CC-486 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) Rate (Cohorts 1 and 2)
CR rate was the percentage of participants who achieved CR (CR without minimal residual disease (CRMRD-) or complete remission with positive or unknown minimal residual disease (CRMRD+/unk)) as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-cancer therapy. CRMRD- and CRMRD+/unk were defined as neutrophils >1.0 ×10^9/L; platelets >100 × 10^9/L and <5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRMRD- status as determined using multiparameter flow cytometry with a sensitivity of < 0.1%. Assessment of leukemia response in participants with acute myeloid leukemia (AML) were conducted based on the European Leukemia Net (ELN) recommendations for AML.
Percentages were rounded-off. Clopper-Pearson method was used for outcome measure analysis.
Measured: Up to 2 years
Minimal Residual Disease Negative Complete Remission Rate (Cohort 3)
The minimal residual disease (MRD) negative CR rate was defined as the percentage of participants who maintain CR as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments, as determined using multiparameter flow cytometry with a sensitivity of < 0.1% while on study prior to initiation of any new anti-AML therapy. Assessment of leukemia response in participants with AML were conducted based on the ELN recommendations for AML. CR was defined in outcome measure #1.
Measured: Up to 2 years
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3)
DLTs were defined as any Grade 4 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (that had worsened in severity from pretreatment baseline) during the 4-week DLT assessment period and was related to magrolimab or magrolimab combination.
Measured: Up to 28 days
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3)
TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dosing date or the day before initiation of new anticancer therapy including SCT, whichever comes first. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Percentages were rounded-off.
Measured: First dose date up to 1.7 years plus 70 days
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3)
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 70 days or the day before initiation of any new anticancer therapy including SCT, whichever comes first. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent.
Percentages were rounded-off.
Measured: First dose date up to 1.7 years plus 70 days
Secondary outcomes (17)
Overall Response Rate (ORR)
ORR was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS as per investigator based on prespecified criteria before starting any new anti-AML therapy (including SCT). CRi and CRh were defined as neutrophils >0.5 x 10^9/L, platelets > 50 x 10^9/L (except residual neutropenia (<1.0 × 10^9/L) or thrombocytopenia (<100 × 109/L) for CRi) and bone marrow blasts <5%; Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. PR: Neutrophils >1.0 x 10^9/L, platelets >100 x 10^9/L, bone marrow blasts reduced to 5%-25%, and a ≥50% reduction from baseline. Blasts <5% with Auer rods may also be considered a PR. MLFS: Bone marrow blasts <5%, absence of circulating blasts or Auer rods, no extramedullary disease, marrow should not merely be "aplastic"; at least 200 cells or 10% cellularity, and no requirement for hematologic recovery. CR was defined in outcome measure #1.
Percentages were rounded-off.
Measured: Up to 2 years
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2)
CR/CRh rate was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk) or CRh as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-AML therapy (including SCT). CR was defined in outcome measure 1. CRh was defined in outcome measure 6. Percentages were rounded-off. Clopper-Pearson exact method was used in outcome measure analysis.
Measured: Up to 2 years
Duration of Response (DOR) (Cohorts 1 and 2)
DOR was measured from the time assessment criteria that were met for CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS, whichever was first recorded, until the first date of AML relapse, progressive disease, or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies.CR was defined in outcome measure #1. CRi, CRh, PR, or MLFS were defined in outcome measure #6.
Kaplan-Meier (KM) estimates were used in outcome measure analysis.
Measured: Up to 2 years
Duration of Complete Remission (DCR) (Cohorts 1 and 2)
DCR was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1.
KM estimates were used in outcome measure analysis.
Measured: Up to 2 years
Duration of CR/CRi (Cohorts 1 and 2)
Duration of CR/CRi was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) or CRi until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRi was defined in outcome measure #6.
KM estimates were used in outcome measure analysis.
Measured: Up to 2 years
Duration of CR/CRh (Cohorts 1 and 2)
Duration of CR/CRh was measured from the time the assessment criteria are first met for CR (CRMRD- or CRMRD+/unk) or CRh until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRh was defined in outcome measure #6.
KM estimates were used in outcome measure analysis.
Measured: Up to 2 years
Event-Free Survival (EFS) (Cohorts 1 and 2)
EFS was defined as the time from the date of the first dose of study treatment to the earliest date of documented relapse from CR, treatment failure (defined as failure to achieve CR during the response assessment window (the first treatment dosing date until before the fifth cycle of magrolimab + venetoclax + azacitidine in Cohort 1 and the first treatment dosing date until before the third cycle of magrolimab + MEC in Cohort 2), or death from any cause within the response assessment window. Response assessments post SCT were included in the analysis. Deaths post SCT or new anti-AML therapies (except SCT and post SCT maintenance) were included. Those who were not observed to have one of these events during the study were censored at the date of their last response assessment during the study. Day 1 of treatment was assigned as the event date for participants with treatment failure. CR was defined in outcome measure #1.
KM estimates were used in outcome measure analysis.
Measured: Up to 2 years
Relapse-Free Survival (RFS) Rate (Cohort 3)
RFS was defined as the time from the first dose of study treatment until the first date of AML relapse or death from any cause, whichever came first.
Measured: Up to 2 years
MRD Negative CR/CRi Rate (Cohort 3)
MRD negative CR/CRi rate was defined as the percentage of participants who maintained CR/CRi as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments as determined using multiparameter flow cytometry with a sensitivity of < 0.1% while on study prior to initiation of any new anti-AML therapy. CR was defined in outcome measure #1. CRi was defined in outcome measure #6.
Measured: Up to 2 years
Duration of Minimal Residual Disease Negative Complete Remission (Cohort 3)
Duration of MRD negative CR was measured from the time the participant achieved MRD-negative status and maintained CR until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1.
Measured: Up to 2 years
Duration of MRD Negative CR/CRi (Cohort 3)
Duration of MRD negative CR/CRi was measured from the time the participant achieved MRD-negative status (first of the 2 consecutive MRD negative bone marrow assessments) and maintained CR/CRi until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1. CRi was defined in outcome measure #6.
Measured: Up to 2 years
Overall Survival (OS) (Cohorts 1, 2 and 3)
OS was measured from the date of the first dose of study treatment to the date of death from any cause. Those who were not observed to die during the study were censored at last date they were known to be alive.
KM estimates were used in outcome measure analysis.
Measured: Up to 2 years
Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3)
RBC transfusion independence rate was the percentage of participants who had a 56-day or longer period with no RBC or whole blood transfusion at any time between the date of the first dose and discontinuation of study treatment among all participants who were RBC transfusion-dependent at baseline. RBC transfusion independence rate was reported as 2 categories:
- Conversion rate: Participants who received an RBC or whole blood transfusion within the 28 days prior to the first dose of study treatment, and were RBC transfusion-independent post-baseline.
- Maintenance rate: Participants who were RBC transfusion independent at baseline and maintained it post-baseline.
Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.
Measured: Up to 2 years
Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3)
Platelet transfusion independence rate was the percentage of participants who had a 56-day or longer period with no platelet transfusions at any time between the date of the first dose and discontinuation of study treatment among all participants who were platelet transfusion-dependent at baseline. Platelet transfusion independence rate was reported as 2 categories:
- Conversion rate: Participants who received an platelet transfusion within 28 days prior to the first dose of study treatment,
- Maintenance rate: Participants who were platelet transfusion independent at baseline and maintained it post-baseline.
Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.
Measured: Up to 2 years
Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3)
Measured: Cohort 1: Predose: Days 1, 8, 29, 57, 113, 169, 253 and 337; Cohort 2: Days 1, 8, 29 and 57
Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Percentages were rounded-off.
Measured: Up to 2 years
Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start28 Jun 2021
- Primary completion4 Mar 2024
- Study completion4 Mar 2024
Why it stopped: Sponsor decision to terminate the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myeloid MalignanciesStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- After completion of Safety Run-in cohorts and identification of the RP2D for the specific cohorts, participants may be enrolled to the corresponding Phase 2 cohorts.
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04778410
- Sponsor's protocol ID
- GS-US-546-5920
- Other IDs
- 2021-003833-13
- Status last verified
- Feb 2025
- First submitted
- 22 Feb 2021
- Last updated
- 20 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Mannis GN, Abboud C, Daver NG, Guru Murthy GS, Wang ES, Bradley TJ, et al. Tolerability and Efficacy of Magrolimab Plus Mitoxantrone, Etoposide, and Cytarabine (MEC) in Patients with Acute Myeloid Leukemia (AML) Refractory/Relapsed (R/R) After Induction Chemotherapy (IC). European Hematology Association (EHA) 13-16 June 2024.
Mannis GN, Abboud CN, Daver NG, Murthy GSG, Wang ES, Bradley TJ, Yaghmour G, Vachhani P, Balasubramanian SK, Chua CC, Fong CY, Asch AS, Dong M, Li S, Bagheri T, Doshi P, Vyas P, Malki MMA. Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia. EJHaem. 2025 May 13;6(3):e70051. doi: 10.1002/jha2.70051. eCollection 2025 Jun.
PubMed 40364806
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT04778410
- Acronym / sponsor ID
- GS-US-546-5920
- Conditions
- Myeloid Malignancies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to terminate the study.
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- 4 Mar 2024 (actual)
- Study completion
- 4 Mar 2024 (actual)
- First posted
- 3 Mar 2021 (actual)
- Results
- Posted 20 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical study is to learn more about the safety and dosing of the study drug, magrolimab (Mag), in combination with anti-leukemia therapies in participants with acute myeloid leukemia (AML).
Detailed description
The anti-leukemia therapies are defined as follows:
- Venetoclax (Ven)
- Azacitidine (Aza)
- Mitoxantrone, etoposide, and cytarabine (MEC)
This study consists of 3 safety run-in cohorts;
- Safety Run-in Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Safety Run-in Cohort 2 (R/R AML Mag + MEC)
- Safety Run-in Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Participants will receive treatment at the assigned dose level for at least 4 cycles in the Safety Run-in cohorts, after which they may continue at the assigned dose level or switch to the RP2D upon agreement between the investigator and the sponsor. After completion of each safety run-in cohort and identification of the RP2D for that cohort, participants may be enrolled into the corresponding Phase 2 cohorts;
- Phase 2 Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Phase 2 Cohort 2 (R/R AML Mag + MEC)
- Phase 2 Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Cycle length is 28 days for both the Safety Run-in and Phase 2 cohorts.
Note: All cohorts are closed to screening and enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- After completion of Safety Run-in cohorts and identification of the RP2D for the specific cohorts, participants may be enrolled to the corresponding Phase 2 cohorts.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine | Experimental | Drug: Magrolimab, Drug: Azacitidine, Drug: VenetoclaxParticipants with newly diagnosed untreated acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then every week (QW) x 5 doses; 30 mg/kg every 2 weeks (Q2W) beginning 1 week after the 5 weekly 30 mg/kg dose in every 28-day cycle along with azacitidine and venetoclax first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. |
| Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine | Experimental | Drug: Magrolimab, Drug: Mitoxantrone, Drug: Etoposide, Drug: CytarabineParticipants with relapsed/refractory (RR) AML after intensive induction chemotherapy will receive magrolimab 1 mg/ on Days 1, 4; 15 mg/kg, on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with mitoxantrone + etoposide + cytarabine (MEC) first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. |
| Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486 | Experimental | Drug: Magrolimab, Drug: CC-486Participants with AML who achieved CR or CRi with MRD positivity following intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with CC-486 as maintenance therapy first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- White blood cell (WBC) count ≤ 20 × 10^3/microliter (μL) prior to first dose of study treatment. If the individual's WBC count is > 20 × 10^3/ μL prior to first dose of study treatment, the individual can be enrolled, assuming all other eligibility criteria are met
- For individuals with prior cardiac history, the hemoglobin must be ≥ 9 grams per deciliter (g/dL) prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility
- Adequate liver function
- Adequate renal function
- Individual has provided informed consent
Key exclusion criteria (14 listed)
- Positive serum pregnancy test
- Breastfeeding female
- Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
- Individuals receiving any live virus vaccine within 4 weeks prior to initiation of study treatments
- Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) -targeting agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MagrolimabAlso: GS-4721Administered intravenously | Drug | Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine, Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine, Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486 |
| AzacitidineAdministered either subcutaneously or IV, 75 mg/milligram per square (m^2) on Days 1 to 7 or Days 1 to 5, 8 and 9 during every cycle | Drug | Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine |
| VenetoclaxAdministered orally at a dose of 100 mg on Day 1, 200 mg on Day 2, 400 mg on Days 3-28 during Cycle 1, followed by 400 mg on Days 1-28 during every cycle | Drug | Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine |
| MitoxantroneAdministered intravenously, 8 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3 | Drug | Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine |
| EtoposideAdministered intravenously, 100 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3 | Drug | Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine |
| CytarabineAdministered intravenously, 1000 mg/m^2 on Days 1-5 during Cycle 1 to Cycle 3 | Drug | Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine |
| CC-486Also: OnuregAdministered orally, 300 mg on Days 1-14 during each cycle | Drug | Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486 |
Primary outcome
Complete Remission (CR) Rate (Cohorts 1 and 2)
Time frame: Up to 2 years
CR rate was the percentage of participants who achieved CR (CR without minimal residual disease (CRMRD-) or complete remission with positive or unknown minimal residual disease (CRMRD+/unk)) as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-cancer therapy. CRMRD- and CRMRD+/unk were defined as neutrophils >1.0 ×10^9/L; platelets >100 × 10^9/L and <5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRMRD- status as determined using multiparameter flow cytometry with a sensitivity of < 0.1%. Assessment of leukemia response in participants with acute myeloid leukemia (AML) were conducted based on the European Leukemia Net (ELN) recommendations for AML. Percentages were rounded-off. Clopper-Pearson method was used for outcome measure analysis.
Minimal Residual Disease Negative Complete Remission Rate (Cohort 3)
Time frame: Up to 2 years
The minimal residual disease (MRD) negative CR rate was defined as the percentage of participants who maintain CR as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments, as determined using multiparameter flow cytometry with a sensitivity of < 0.1% while on study prior to initiation of any new anti-AML therapy. Assessment of leukemia response in participants with AML were conducted based on the ELN recommendations for AML. CR was defined in outcome measure #1.
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3)
Time frame: Up to 28 days
DLTs were defined as any Grade 4 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (that had worsened in severity from pretreatment baseline) during the 4-week DLT assessment period and was related to magrolimab or magrolimab combination.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3)
Time frame: First dose date up to 1.7 years plus 70 days
TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dosing date or the day before initiation of new anticancer therapy including SCT, whichever comes first. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Percentages were rounded-off.
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3)
Time frame: First dose date up to 1.7 years plus 70 days
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 70 days or the day before initiation of any new anticancer therapy including SCT, whichever comes first. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent. Percentages were rounded-off.
17 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 2 years
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2)
Time frame: Up to 2 years
Duration of Response (DOR) (Cohorts 1 and 2)
Time frame: Up to 2 years
Duration of Complete Remission (DCR) (Cohorts 1 and 2)
Time frame: Up to 2 years
Duration of CR/CRi (Cohorts 1 and 2)
Time frame: Up to 2 years
Duration of CR/CRh (Cohorts 1 and 2)
Time frame: Up to 2 years
Event-Free Survival (EFS) (Cohorts 1 and 2)
Time frame: Up to 2 years
Relapse-Free Survival (RFS) Rate (Cohort 3)
Time frame: Up to 2 years
MRD Negative CR/CRi Rate (Cohort 3)
Time frame: Up to 2 years
Duration of Minimal Residual Disease Negative Complete Remission (Cohort 3)
Time frame: Up to 2 years
Duration of MRD Negative CR/CRi (Cohort 3)
Time frame: Up to 2 years
Overall Survival (OS) (Cohorts 1, 2 and 3)
Time frame: Up to 2 years
Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3)
Time frame: Up to 2 years
Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3)
Time frame: Up to 2 years
Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3)
Time frame: Cohort 1: Predose: Days 1, 8, 29, 57, 113, 169, 253 and 337; Cohort 2: Days 1, 8, 29 and 57
Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Time frame: Up to 2 years
Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundMannis GN, Abboud C, Daver NG, Guru Murthy GS, Wang ES, Bradley TJ, et al. Tolerability and Efficacy of Magrolimab Plus Mitoxantrone, Etoposide, and Cytarabine (MEC) in Patients with Acute Myeloid Leukemia (AML) Refractory/Relapsed (R/R) After Induction Chemotherapy (IC). European Hematology Association (EHA) 13-16 June 2024.
- Derived from this study: PubMed 40364806Mannis GN, Abboud CN, Daver NG, Murthy GSG, Wang ES, Bradley TJ, Yaghmour G, Vachhani P, Balasubramanian SK, Chua CC, Fong CY, Asch AS, Dong M, Li S, Bagheri T, Doshi P, Vyas P, Malki MMA. Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia. EJHaem. 2025 May 13;6(3):e70051. doi: 10.1002/jha2.70051. eCollection 2025 Jun.
- Gilead Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
21 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Magrolimab, Azacitidine and Venetoclax in people with Myeloid Malignancies, run by Gilead Sciences at 21 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission (CR) Rate (Cohorts 1 and 2) (time frame: Up to 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04778410, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.