Study of Magrolimab Combinations in Participants With Myeloid Malignancies

  • STATUS
    Recruiting
  • End date
    Mar 6, 2024
  • participants needed
    164
  • sponsor
    Gilead Sciences
Updated on 10 October 2021

Summary

The primary objectives of this study are to evaluate the safety, tolerability and to determine the recommended Phase 2 dose (RP2D) of magrolimab (Mag) in combination with the anti-leukemia therapies of venetoclax (Ven) and azacitidine (Aza) (Cohort 1), mitoxantrone, etoposide, and cytarabine (MEC) (Cohort 2) and CC-486 (Cohort 3) respectively in participants with acute myeloid leukemia (AML), to evaluate the efficacy of magrolimab in combination with the anti-leukemia therapies as determined by the rate of complete remission (CR) (Phase 2 Cohorts 1 and 2), and/or complete remission with incomplete hematologic recovery (CRi) (CR/CRi) (Phase 2 Cohort 2) and to evaluate the efficacy of magrolimab in combination with anti-leukemia therapy CC-486 as determined by the minimal residual disease (MRD) negative CR rate (Phase 2 Cohort 3).

Description

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 will be enrolled into the corresponding Phase 2 cohorts;

  • Phase 2 Cohort 1 (1L Unfit UML 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.

Details
Condition Myeloid Malignancies
Treatment cytarabine, etoposide, Mitoxantrone, Azacitidine, CC-486, venetoclax, Magrolimab
Clinical Study IdentifierNCT04778410
SponsorGilead Sciences
Last Modified on10 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

All Individuals
White blood cell (WBC) count 20 10^3/microliter (L) prior to first dose of study treatment. If the individual's WBC count is > 20 10^3/ L 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 9.5 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
years of age
to 74 years of age with at least 1 of the following comorbidities
ECOG performance status of 2 or 3
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
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 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 histological confirmation of AML by WHO criteria who are refractory to or have experienced first relapse after initial intensive chemotherapy
At least 3 weeks must have elapsed since any prior systemic or targeted anti-leukemia agents. NOTE: Localized non-central nervous system (CNS) radiotherapy, hydroxyurea, oral etoposide, 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
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

Exclusion Criteria

Positive serum pregnancy test
Breastfeeding female
Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRP) -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-AML therapies and who are in complete remission for over 3 years. 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
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