Study of Magrolimab Combinations in Participants With Myeloid Malignancies

NCT04778410 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-546-59202021-003833-13
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 21

Brief 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).

Conditions

Myeloid Malignancies

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  First dose date up to 1.7 years plus 70 days

Secondary Outcomes (17)

• Overall Response Rate (ORR)

  Up to 2 years

• Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2)

  Up to 2 years

• Duration of Response (DOR) (Cohorts 1 and 2)

  Up to 2 years

• Duration of Complete Remission (DCR) (Cohorts 1 and 2)

  Up to 2 years

• Duration of CR/CRi (Cohorts 1 and 2)

  Up to 2 years

Study Arms (3)

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.

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.

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.

Drug: Magrolimab; Drug: CC-486

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: GS-4721

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

Azacitidine DRUG

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

Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine

Venetoclax DRUG

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

Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine

Mitoxantrone DRUG

Administered intravenously, 8 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3

Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine

Etoposide DRUG

Administered intravenously, 100 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3

Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine

Cytarabine DRUG

Administered intravenously, 1000 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3

Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine

CC-486 DRUG

Administered orally, 300 mg on Days 1-14 during each cycle

Also known as: Onureg

Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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%

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

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

Duarte, California, 91010, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Stanford Cancer Center

Palo Alto, California, 94305, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

OU Health, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Oxford University Hospitals NHS Foundation Trust, Churchill Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• 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.

  BACKGROUND

• 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.

  PMID: 40364806 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

magrolimab; Azacitidine; venetoclax; Mitoxantrone; Etoposide; Cytarabine; cc-486

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Arabinonucleosides

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: 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.

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 3, 2021
• Study Start: June 28, 2021
• Primary Completion: March 4, 2024
• Study Completion: March 4, 2024
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); GB (1); US (17)