AML
Conditions
Interventions
Magrolimab 1 mg/kg intravenous (IV)
Magrolimab 15 mg/kg IV
Magrolimab 30 mg/kg IV
In combination with:
Venetoclax 10 mg oral
Venetoclax 50 mg oral
Venetoclax 100 mg oral
Venetoclax 200 mg oral
Venetoc
Sponsors
Gilead Sciences
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Previously untreated patients with histological confirmation of AML by 2016 World Health Organization criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. Patients must be considered ineligible for intensive chemotherapy, defined by the following: a)>= 75 years of age; Or b)>= 18 to 74 years of age with at least 1 of the following comorbidities: i) Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 ii)Diffusing capacity of the lung of carbon monoxide = 30 mL/min to 1.5 ** upper limit of normal (ULN) vi) Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy that must be approved by the sponsor*s medical monitor before study enrollment 2) ECOG performance status: a)Of 0 to 2 for subjects >= 75 years of age Or b)Of 0 to 3 for subjects >= 18 to 74 years of age 3)Patients with white blood cell (WBC) count 20x10*3/µL prior to randomization, the patient can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be = 9 g/dL prior to initial dose of study treatment based on complete blood count result. NOTE: Transfusions are allowed to meet hemoglobin eligibility. 5) Patient has provided informed consent. 6) Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol. 7) Male or female, >= 18 years of age 8) Patients must have adequate renal function as demonstrated by a creatinine clearance >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection. 9) Adequate liver function as demonstrated by: a)aspartate aminotransferase = 18 to 74 years of age may have total bilirubin
Exclusion criteria
Exclusion criteria: 1) Positive serum pregnancy test 2) Breastfeeding female 3) Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient. 4) Patients receiving any live vaccine within 4 weeks prior to initiation of study treatments. 5) Prior treatment with any of the following: a) CD47 or signal regulatory protein alpha-targeting agents b) Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea NOTE: Patients with prior myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) who have not received prior HMAs or venetoclax or chemotherapeutic agents for MDS/MPN may be enrolled in the study. Prior treatment with MDS/MPN therapies including, but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell (RBC-), WBC-, or platelet-direct therapies or growth factors is allowed for these patients. 6) Current participation in another interventional clinical study 7) Known inherited or acquired bleeding disorders 8) Patients who have received treatment with strong and/or moderate CYP3A inducers (eg, preparations containing St. John*s wort) within 7 days prior to the initiation of study treatments 9) Patients 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 and are unwilling to discontinue consumption of these throughout the receipt of study drug 10) Patients who have malabsorption syndrome or other conditions that preclude enteral route of administration 11) Clinical suspicion of or documented active central nervous system (CNS) involvement with AML 12) Patients who have acute promyelocytic leukemia 13) 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 uncontrolled infection, and congestive heart failure New York Heart Association Class III to IV. 14) Known history, diagnosis, or suspicion of Hemophagocytic Lymphohistiocytosis (HLH) syndrome. 15) 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. NOTE: Localized non-CNS radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy 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. 16) Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or HIV infection in medical history within 3 months of study entry. 17) Active HBV, and/or active HCV, and/or HIV following testing at screening: a) Patients who test positive for hepatitis B surface
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is OS. Two interim OS analyses will be conducted, the first one after 121 deaths (40% of the expected 303 deaths), and the second one after 227 deaths (75% of the expected 303 deaths) are observed among all patients; the primary OS analysis will be conducted after 303 deaths have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Rate of CR + CRh within 6 cycles of treatment • Rate of CR within 6 cycles of treatment • EFS • Duration of CR + CRh in patients who achieved CR or CRh within 6 cycles of treatment • DCR in patients who achieved CR within 6 cycles of treatment • Rate of CR/CRhMRD- within 6 cycles of treatment • Rate of CRMRD- within 6 cycles of treatment • Transfusion independence conversion rate • TTD on the GHS/QoL and the physical functioning scales of the EORTC QLQ-C30 • Incidence of treatment-emergent adverse events (AEs) and clinical laboratory abnormalities during the study • Magrolimab serum concentrations over time • Incidence/prevalence rate and magnitude of anti-magrolimab antibodies in serum Exploratory study parameters/outcome of the study: • Transfusion independence maintenance rate • TTD on the EORTC QLQ-C30 pain, fatigue, role functioning, emotional functioning, social functioning, and cognitive functioning scales and single items • Mean change from baseline on the EORTC QLQ-C30 domains, the EQ-VAS, and PGIS scale • Descriptive summaries on the EQ-5D-5L descriptive system and PGIS/PGIC scales • ORR within 6 cycles of treatment • Rate of CR/CRiMRD- within 6 cycles of treatment • Rate of CR + CRi within 6 cycles of treatment • EFS (including CR and CRh) • Rate of hematological improvement • DOR in patients who achieved response within 6 cycles of treatment • Duration of CR + CRi achieved within 6 cycles of treatment • Rate of MRD negativity in patients with CR + CRi • Rate of MRD negativity in patients with CR + CRh • Rate of MRD negativity in patients with CR + CRi • Rate of MRD negativity by flow cytometry and NGS, and concordance between methods • Rate of SCT • 30- and 60-day mortality rate • Changes and percentage changes from baseline of biomarkers including biomarkers of immune cell recruitment or of immune cell signaling • Biomarkers related to resistance, including mutational profile of leukemic clones, and immune profil | — |
Countries
Netherlands
Outcome results
None listed