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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04778410




Registration number
NCT04778410
Ethics application status
Date submitted
22/02/2021
Date registered
3/03/2021

Titles & IDs
Public title
Study of Magrolimab Combinations in Participants With Myeloid Malignancies
Scientific title
A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Myeloid Malignancies
Secondary ID [1] 0 0
2021-003833-13
Secondary ID [2] 0 0
GS-US-546-5920
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myeloid Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Azacitidine
Treatment: Drugs - Venetoclax
Treatment: Drugs - Mitoxantrone
Treatment: Drugs - Etoposide
Treatment: Drugs - Cytarabine
Treatment: Drugs - CC-486

Experimental: Safety Run-in Cohort 1 (1L Unfit AML Mag+Ven+Aza) - Participants with newly diagnosed untreated AML who are ineligible for intensive induction chemotherapy will receive magrolimab, venetoclax and azacitidine.

Experimental: Safety Run-in Cohort 2 (R/R AML Mag+MEC) - Participants with relapsed or refractory (r/r) AML will receive magrolimab and MEC.

Experimental: Safety Run-in Cohort 3 (Post-Chemo Maintenance Mag+CC-486) - Participants with newly diagnosed AML who are in complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with minimal residual disease (MRD) positivity following intensive chemotherapy will receive magrolimab and CC-486.

Experimental: Phase 2 Cohort 1 (1L Unfit AML Mag+Ven+Aza) - Participants with newly diagnosed untreated AML who are ineligible for intensive induction chemotherapy will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety run-in cohort 1, venetoclax and azacitidine.

Experimental: Phase 2 Cohort 2 (R/R AML Mag+MEC) - Participants with relapsed or refractory (r/r) AML will receive magrolimab at the RP2D determined in the Safety run-in cohort 2 and MEC.

Experimental: Phase 2 Cohort 3 (Post-Chemo Maintenance Mag+CC-486) - Participants with newly diagnosed AML who are in complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with minimal residual disease (MRD) positivity following intensive chemotherapy will receive magrolimab at the RP2D determined in the Safety run-in cohort 3 and CC-486.


Treatment: Drugs: Magrolimab
Administered intravenously

Treatment: Drugs: Azacitidine
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

Treatment: Drugs: Venetoclax
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

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

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

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

Treatment: Drugs: CC-486
Administered orally, 300 mg on Days 1-14 during each cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Complete Remission (CR) (Phase 2 Cohorts 1 and 2)
Timepoint [1] 0 0
First dose date up to 3 years
Primary outcome [2] 0 0
Minimal Residual Disease Negative Complete Remission Rate (Phase 2 Cohort 3)
Timepoint [2] 0 0
First dose date up to 5 years
Primary outcome [3] 0 0
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Safety Run-in Cohorts 1, 2, and 3)
Timepoint [3] 0 0
First dose date up to 28 days of the first dosing cycle
Primary outcome [4] 0 0
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE's) According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts 1, 2, and 3)
Timepoint [4] 0 0
Safety Run-in Cohorts 1 and 3: First dose date up to 24 months plus 70 days; Safety Run-in Cohort 2: First dose date up to 12 months plus 70 days
Primary outcome [5] 0 0
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Safety Run-in Cohorts 1, 2, and 3)
Timepoint [5] 0 0
Safety Run-in Cohorts 1 and 3: First dose date up to 24 months plus 70 days; Safety Run-in Cohort 2: First dose date up to 12 months plus 70 days
Secondary outcome [1] 0 0
Overall Response Rate (ORR) including Complete Remission/Complete Remission with Incomplete Hematologic Recovery (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [1] 0 0
First dose date up to 3 years
Secondary outcome [2] 0 0
Complete Remission or Complete Remission with Partial Hematologic Recovery Rate (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [2] 0 0
First dose date up to 3 years
Secondary outcome [3] 0 0
Duration of Response (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [3] 0 0
First dose date up to 3 years
Secondary outcome [4] 0 0
Duration of Complete Remission (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [4] 0 0
First dose date up to 3 years
Secondary outcome [5] 0 0
Duration of Complete Remission or Complete Remission with Incomplete Hematologic Recovery (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [5] 0 0
First dose date up to 3 years
Secondary outcome [6] 0 0
Duration of Complete Remission or Complete Remission with Partial Hematologic Recovery (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [6] 0 0
First dose date up to 3 years
Secondary outcome [7] 0 0
Event-Free Survival (Safety Run-in Cohorts 1 and 2; Phase 2 Cohorts 1 and 2)
Timepoint [7] 0 0
First dose date up to 3 years
Secondary outcome [8] 0 0
Relapse-Free Survival (Safety Run-in Cohort 3; Phase 2 Cohort 3)
Timepoint [8] 0 0
First dose date up to 5 years
Secondary outcome [9] 0 0
Minimal Residual Disease Negative Complete Remission or Complete Remission with Incomplete Hematologic Recovery (Safety Run-in Cohort 3; Phase 2 Cohort 3)
Timepoint [9] 0 0
First dose date up to 5 years
Secondary outcome [10] 0 0
Duration of Minimal Residual Disease Negative Complete Remission (Safety Run-in Cohort 3; Phase 2 Cohort 3)
Timepoint [10] 0 0
First dose date up to 5 years
Secondary outcome [11] 0 0
Duration of Minimal Residual Disease Negative Complete Remission or Complete Remission with Incomplete Hematologic Recovery (Safety Run-in Cohort 3; Phase 2 Cohort 3)
Timepoint [11] 0 0
First dose date up to 5 years
Secondary outcome [12] 0 0
Overall Survival (OS) (Safety Run-in Cohorts 1, 2, and 3; Phase 2 Cohorts 1, 2, and 3)
Timepoint [12] 0 0
Safety Run-in Cohorts 1 and 2: First dose date up to 3 years; Safety Run-in Cohort 3: First dose date up to 5 years; Phase 2 Cohorts 1 and 2: First dose date up to 3 years; Phase 2 Cohort 3: First dose date up to 5 years
Secondary outcome [13] 0 0
Red Blood Cell Transfusion Independence Rate (Safety Run-in Cohorts 1, 2, and 3; Phase 2 Cohorts 1, 2, and 3)
Timepoint [13] 0 0
Safety Run-in Cohorts 1 and 3: First dose date up to 24 months; Safety Run-in Cohort 2: First dose date up to 12 months; Phase 2 Cohorts 1 and 3: First dose date up to 24 months; Phase 2 Cohort 2: First dose date up to 12 months
Secondary outcome [14] 0 0
Platelet Transfusion Independence Rate (Safety Run-in Cohorts 1, 2, and 3; Phase 2 Cohorts 1, 2, and 3)
Timepoint [14] 0 0
Safety Run-in Cohorts 1 and 3: First dose date up to 24 months; Safety Run-in Cohort 2: First dose date up to 12 months; Phase 2 Cohorts 1 and 3: First dose date up to 24 months; Phase 2 Cohort 2: First dose date up to 12 months
Secondary outcome [15] 0 0
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) According to the NCI CTCAE Version 5.0 (Phase 2 Cohorts 1, 2, and 3)
Timepoint [15] 0 0
Phase 2 Cohorts 1 and 3: First dose date up to 24 months plus 70 days; Phase 2 Cohort 2: First dose date up to 12 months plus 70 days
Secondary outcome [16] 0 0
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0 (Phase 2 Cohorts 1, 2, and 3)
Timepoint [16] 0 0
Phase 2 Cohorts 1 and 3: First dose date up to 24 months plus 70 days; Phase 2 Cohort 2: First dose date up to 12 months plus 70 days
Secondary outcome [17] 0 0
Plasma Concentration of Magrolimab in Combination with Anti-leukemia Therapy (Safety Run-in Cohorts 1, 2, and 3; Phase 2 Cohorts 1, 2, and 3)
Timepoint [17] 0 0
Within 72 hours predose & 12 hours postdose before subsequent doses of magrolimab on Days 1 & 8 of Cycle 1, Day 1 of Cycles 2, 3, 5, 7, 10, 13, and end of treatment (EOT) (within 7 days after last dose of magrolimab or EOT decision); Cycle length=28 days
Secondary outcome [18] 0 0
Immunogenicity of Magrolimab in Combination with Anti-leukemia Therapy (Safety Run-in Cohorts 1, 2, and 3; Phase 2 Cohorts 1, 2, and 3)
Timepoint [18] 0 0
Within 72 hours predose & 12 hours postdose before subsequent doses of magrolimab on Day 1 of Cycles 1, 2, 3, 5, 7, 10, 13, and end of treatment (EOT) (within 7 days after last dose of magrolimab or EOT decision); Cycle length=28 days

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 (SIRPa) -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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.