Study Details

PROTOCOL 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).

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Myeloid Malignancies

Gender

N/A

Date

June 2021 - March 2024

Study Type

INTERVENTIONAL

Study Phase

PHASE2

Product

Magrolimab, Azacitidine, Venetoclax, Mitoxantrone, Etoposide, Cytarabine, CC-486

Eligibility Information

Inclusion Criteria

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%
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

Exclusion Criteria

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
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.

Locations

Locations (21)

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

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

Duarte, California, United States, 91010

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, United States, 90048

Stanford Cancer Center

Palo Alto, California, United States, 94305

Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

The University of Chicago Medical Center

Chicago, Illinois, United States, 60637

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

OU Health, Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

Baylor University Medical Center

Dallas, Texas, United States, 75246

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Austin Health

Heidelberg, Victoria, Australia, 3084

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

Oxford University Hospitals NHS Foundation Trust, Churchill Hospital

Oxford, United Kingdom, OX3 9DU

Study of Magrolimab Combinations in Participants With Myeloid Malignancies

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