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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05079230




Registration number
NCT05079230
Ethics application status
Date submitted
4/10/2021
Date registered
15/10/2021
Date last updated
16/04/2024

Titles & IDs
Public title
Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy
Secondary ID [1] 0 0
2021-003434-36
Secondary ID [2] 0 0
GS-US-590-6154
Universal Trial Number (UTN)
Trial acronym
ENHANCE-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Magrolimab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine
Treatment: Drugs - Magrolimab Placebo

Experimental: Magrolimab + Venetoclax + Azacitidine - Participants will receive
magrolimab: 1 mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and then every week for 5 doses and every 2 weeks thereafter
venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.

Placebo Comparator: Magrolimab Placebo + Venetoclax + Azacitidine - Participants will receive
magrolimab placebo: Days 1, 4, 8, 11, and 15, then every week for 5 doses and every 2 weeks thereafter
venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter
azacitidine: 75 mg/m^2 on Days 1-7 or Days 1-5 and 8-9 of each cycle
Each cycle is 28 days.


Treatment: Drugs: Magrolimab
Administered intravenously (IV)

Treatment: Drugs: Venetoclax
Tablets administered orally

Treatment: Drugs: Azacitidine
Administered according to region-specific drug labeling, either subcutaneously (SC) or intravenously (IV)

Treatment: Drugs: Magrolimab Placebo
Administered intravenously (IV)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization up to death or end of study (up to 5 years) whichever occurs first
Secondary outcome [1] 0 0
Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh)
Timepoint [1] 0 0
Up to 7 months
Secondary outcome [2] 0 0
Rate of Complete Remission (CR)
Timepoint [2] 0 0
Up to 7 months
Secondary outcome [3] 0 0
Event-Free Survival (EFS)
Timepoint [3] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [4] 0 0
Duration of CR + CRh in Participants who achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Duration of Complete Remission (DCR) in Participants who achieved Complete Remission (CR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Rate of CR/Complete Remission With Partial Hematologic Recovery Without Minimal Residual Disease (CRhMRD-)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Rate of Complete Remission Without Minimal Residual Disease (CRMRD-)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Transfusion Independence Conversion Rate
Timepoint [8] 0 0
First dose date up to End of Treatment (EOT) (up to 5 years)
Secondary outcome [9] 0 0
Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale
Timepoint [9] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [10] 0 0
TTD on the EORTC QLQ-C30 Physical Functioning Scale
Timepoint [10] 0 0
Randomization up to end of study (up to 5 years)
Secondary outcome [11] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Timepoint [11] 0 0
First dose date up to last dose date (up to 5 years) plus 70 days
Secondary outcome [12] 0 0
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Timepoint [12] 0 0
First dose date up to last dose date (up to 5 years) plus 70 days
Secondary outcome [13] 0 0
Serum Concentration of Magrolimab over time
Timepoint [13] 0 0
First dose date up to EOT (up to 5 years)
Secondary outcome [14] 0 0
Rate of Anti-Magrolimab Antibody Incidence
Timepoint [14] 0 0
First dose date up to EOT (up to 5 years)
Secondary outcome [15] 0 0
Magnitude of Anti-Magrolimab Antibody Incidence
Timepoint [15] 0 0
First dose date up to EOT (up to 5 years)

Eligibility
Key inclusion criteria
Key

- Previously untreated individuals with histological confirmation of acute myeloid
leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for
treatment with a standard cytarabine and anthracycline induction regimen due to age,
or comorbidity. Individuals must be considered ineligible for intensive chemotherapy,
defined by the following:

- = 75 years of age; Or

- = 18 to 74 years of age with at least 1 of the following comorbidities:

- Eastern Cooperative Oncology Group (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 = 50%

- Baseline creatinine clearance = 30 mL/min to < 45 mL/min calculated by the
Cockcroft Gault formula or measured by 24-hour urine collection

- Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)

- Any other comorbidity that the investigator judges to be incompatible with
intensive chemotherapy

- ECOG performance status:

- Of 0 to 2 for individuals = 75 years of age Or

- Of 0 to 3 for individuals = 18 to 74 years of age

- Individuals with white blood cell (WBC) count = 20 x 10^3/µL prior to randomization.
If the individual's WBC is > 20 x10^3/µL prior to randomization, the individual can be
enrolled, assuming all other eligibility criteria are met. However, the WBC should be
= 20 x 10^3/µL prior to the first dose of study treatment and prior to each
magrolimab/placebo dose during Cycle 1.

- Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to
randomization and throughout the study to reduce the WBC to = 20 x 10^3/µL to
enable eligibility for study drug dosing

- Hemoglobin must be = 9 g/dL prior to initial dose of study treatment

- Note: Transfusions are allowed to meet hemoglobin eligibility

- Pretreatment blood cross-match completed

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with any of the following:

- cluster of differentiation 47 (CD47) or signal regulatory protein alpha
(SIRPa)-targeting agents

- Antileukemic therapy for the treatment of AML (eg, hypomethylating agents (HMAs),
low-dose cytarabine, and/or venetoclax), excluding hydroxyurea

- Note: Individuals with prior MDS who have not received prior HMAs or
venetoclax or chemotherapeutic agents for MDS may be enrolled in the study.
Prior treatment with myelodysplastic syndrome (MDS) therapies including, but
not limited to lenalidomide, erythroid-stimulating agents, or similar red
blood cell negative (RBC-), white blood cell negative (WBC-), or
platelet-direct therapies or growth factors is allowed for these
individuals.

- Clinical suspicion of or documented active central nervous system (CNS) involvement
with AML

- Individuals who have acute promyelocytic leukemia

- 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 anticancer therapies and have had no evidence of active malignancy for
at least 1 year

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/04/2024
Sample size
Target
Accrual to date
Final
378
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Woden
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
St George Hospital, Clinical Research Unit Haemotology, Division of Cancer Services - Sydney
Recruitment hospital [6] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [7] 0 0
Monash University, Eastern Health-Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
Northern Health - Epping
Recruitment hospital [9] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2606 - Woden
Recruitment postcode(s) [2] 0 0
2640 - Albury
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2217 - Sydney
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3076 - Epping
Recruitment postcode(s) [9] 0 0
3000 - Melbourne
Recruitment outside Australia
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United States of America
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Arkansas
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Maryland
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Massachusetts
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Missouri
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Oregon
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Valencia
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Wolverhampton

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

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this clinical study is to compare the study drugs, magrolimab + venetoclax +
azacitidine, versus placebo + venetoclax + azacitidine in participants with untreated acute
myeloid leukemia (AML) who are not able to have chemotherapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05079230
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05079230