Register a trial

Reset your password and enable multi-factor authentication (MFA)


For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.


  1. Go to the Login page, click ‘reset password’ and follow the instructions.
  2. Check your email for the link to set a new password.
  3. Create a new password that meets requirements. New passwords must include at least one lowercase letter, one uppercase letter, one number and one special character (e.g. !#$%&@).
  4. Return to the Login page and enter your new password. A verification code will be sent to your email.
  5. Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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: Cohort 1 (1L Unfit AML): Magrolimab + Venetoclax + Azacitidine - Participants with newly diagnosed untreated acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then every week (QW) x 5 doses; 30 mg/kg every 2 weeks (Q2W) beginning 1 week after the 5 weekly 30 mg/kg dose in every 28-day cycle along with azacitidine and venetoclax first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment.

Experimental: Cohort 2 (R/R AML): Magrolimab + Mitoxantrone + Etoposide + Cytarabine - Participants with relapsed/refractory (RR) AML after intensive induction chemotherapy will receive magrolimab 1 mg/ on Days 1, 4; 15 mg/kg, on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with mitoxantrone + etoposide + cytarabine (MEC) first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment.

Experimental: Cohort 3 (Post-Chemo Maintenance): Magrolimab + CC-486 - Participants with AML who achieved CR or CRi with MRD positivity following intensive induction chemotherapy will receive magrolimab 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose along with CC-486 as maintenance therapy first in the Safety Run-in Cohort. Once the safety of recommended dose of magrolimab is confirmed, the participants in Phase 2 Cohort will be enrolled to receive the treatment.


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
Complete Remission (CR) Rate (Cohorts 1 and 2)
Timepoint [1] 0 0
Up to 2 years
Primary outcome [2] 0 0
Minimal Residual Disease Negative Complete Remission Rate (Cohort 3)
Timepoint [2] 0 0
Up to 2 years
Primary outcome [3] 0 0
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3)
Timepoint [3] 0 0
Up to 28 days
Primary outcome [4] 0 0
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3)
Timepoint [4] 0 0
First dose date up to 1.7 years plus 70 days
Primary outcome [5] 0 0
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3)
Timepoint [5] 0 0
First dose date up to 1.7 years plus 70 days
Secondary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Duration of Response (DOR) (Cohorts 1 and 2)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Duration of Complete Remission (DCR) (Cohorts 1 and 2)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Duration of CR/CRi (Cohorts 1 and 2)
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Duration of CR/CRh (Cohorts 1 and 2)
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Event-Free Survival (EFS) (Cohorts 1 and 2)
Timepoint [7] 0 0
Up to 2 years
Secondary outcome [8] 0 0
Relapse-Free Survival (RFS) Rate (Cohort 3)
Timepoint [8] 0 0
Up to 2 years
Secondary outcome [9] 0 0
MRD Negative CR/CRi Rate (Cohort 3)
Timepoint [9] 0 0
Up to 2 years
Secondary outcome [10] 0 0
Duration of Minimal Residual Disease Negative Complete Remission (Cohort 3)
Timepoint [10] 0 0
Up to 2 years
Secondary outcome [11] 0 0
Duration of MRD Negative CR/CRi (Cohort 3)
Timepoint [11] 0 0
Up to 2 years
Secondary outcome [12] 0 0
Overall Survival (OS) (Cohorts 1, 2 and 3)
Timepoint [12] 0 0
Up to 2 years
Secondary outcome [13] 0 0
Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3)
Timepoint [13] 0 0
Up to 2 years
Secondary outcome [14] 0 0
Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3)
Timepoint [14] 0 0
Up to 2 years
Secondary outcome [15] 0 0
Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3)
Timepoint [15] 0 0
Cohort 1: Predose: Days 1, 8, 29, 57, 113, 169, 253 and 337; Cohort 2: Days 1, 8, 29 and 57
Secondary outcome [16] 0 0
Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Timepoint [16] 0 0
Up to 2 years
Secondary outcome [17] 0 0
Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Timepoint [17] 0 0
Up to 2 years

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 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

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/03/2024
Sample size
Target
Accrual to date
Final
54
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


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04778410