Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical 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).
Phase
Phase 2
Funding Agency/Sponsor
Industrial
Disease
Leukemia
Enrollment Eligibility
Key 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 AML Mag+Ven+Aza)]:
- 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 Mag+MEC)]:
- Individuals with confirmation of AML by WHO criteria who are refractory to or have
experienced first relapse after initial intensive chemotherapy. Note: Patients who are
relapsed after or are refractory to more than 1 line of anti-AML treatment are not
eligible. Patients 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.
- Patients 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 Mag+CC-486):
- Individuals with histological confirmation of AML by WHO criteria who achieved a CR or
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
Key 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.