A Phase 2 Study of Magrolimab Combinations in Myeloid Malignancies
Research type
Research Study
Full title
A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients with Myeloid Malignancies
IRAS ID
298230
Contact name
Paresh Vyas
Contact email
Sponsor organisation
Gilead Sciences, Inc.
Eudract number
2021-003833-13
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
147229, IND number
Duration of Study in the UK
2 years, 6 months, days
Research summary
Research Summary
This study will test an experimental medication named magrolimab in combination with other medications for the treatment of myeloid malignancies. The purpose of this study is to evaluate the safety, tolerability and efficacy magrolimab in combination with other therapies for participants who have been newly diagnosed with acute myeloid leukaemia (AML) and are unfit for intensive chemotherapy, have relapsed refractory AML, or have Minimal Residual Disease (MRD)-positive AML disease.
In this study, participants may receive one of the following medication combinations:
• Cohort 1: magrolimab, venetoclax and azacitidine
• Cohort 2: magrolimab, mitoxantrone, etoposide, and cytarabine
• Cohort 3: magrolimab and CC- 486 (Onureg)This is an open-label study where both participant and the study doctor will know what study medication has been assigned.
The study treatment will be given in 28-day (4-week) cycles. Participants in Cohorts 1 and 3 will continue treatment until the study doctor determines that they should discontinue. If participants continue study treatment for 18 months, they will be required to visit the clinic around 59 times. Participants in Cohort 2 will receive study treatment for up to 12 months and will be required to visit the clinic around 41 times. Study procedures include physical examinations, pregnancy tests, collection of blood, bone marrow and buccal swab samples 12-lead electrocardiogram, echocardiogram, or multigated acquisition (scan).
The study will include about 164 participants at about 35 locations globally.
Gilead Sciences, Inc. is the Sponsor for this study.Summary of Results
General information about the study What is myeloid malignancy?
Myeloid malignancy (myeloid cancer) is a type of blood cancer where the bone marrow is unable to make healthy blood cells. Bone marrow, a spongy tissue in the middle of bones, makes myeloid stem cells (immature cells). These cells mature into different types of blood cells. In myeloid cancer, these myeloid stem cells become faulty and do not mature into healthy blood cells. One type of myeloid cancer is acute myeloid leukemia (AML). AML is a fast-growing cancer. If left untreated, people with AML may die.
Existing treatments do not always work well for people with newly diagnosed, untreated, relapsed (R), or refractory (R) AML or for people who have recovered and need maintenance therapy for AML. Relapsed means cancer has come back, and refractory means cancer has stopped responding to the treatment. Therefore, new treatment options are needed for these types of cancers.
Magrolimab is an investigational drug. It is a monoclonal antibody (MAb). MAbs are proteins made in a lab to help the body fight diseases like cancer. In this study, the researchers assessed the use of magrolimab in combination with other chemotherapy medicines for treating AML.
Chemotherapy is a combination of medicines used to kill cancer cells. In this study, chemotherapy medicines commonly used for AML, such as azacitidine, venetoclax, MEC (mitoxantrone, etoposide, and cytarabine), and CC-486 (oral azacitidine), were tested in combination with magrolimab.
What was the purpose of the study?
The purpose of this study was to find a safe dose of magrolimab that can be given in combination with other chemotherapy medicines in different groups of people with AML. The study further assessed the safety and effectiveness of these combinations using a safe and tolerable dose of magrolimab in participants in these groups.
The main questions the researchers wanted to answer in this study were:
• How many participants achieved complete remission (CR) or maintained CR with no disease (minimum residual disease negative, MRD- status)?
CR means the cancer has completely gone away per the study doctor’s assessment.
• How many participants had dose-limiting toxicities (DLTs) in the study, if any?
DLTs were the side effects that were serious enough to prevent further increase in the dose. This was done to find a safe dose of magrolimab to be given with other drugs.
• How many participants had any unwanted medical events (also called Treatment Emergent Adverse Events [TEAEs]) and abnormalities in their laboratory test results during the study?
TEAEs were any unwanted signs or symptoms that participants had during the study. They may or may not be caused by the study treatment. Abnormalities in laboratory test results means the test results lied outside the laboratory reference ranges.
AEs or abnormalities in laboratory test results were considered treatment-emergent if they started or worsened during the treatment period until 70 days after the last dose.
• What side effects did participants have during the study, if any?
Side effects were the TEAEs that the study doctors thought might be caused by the study treatment.
Who took part in the study?
The study began in June 2021 and ended in March 2024. The study was planned to enroll 164 participants, however, only 54 participants from the United States, Australia, and the United Kingdom took part in the study. Participants enrolled in the study were between the ages of 22 to 84 years. Out of 54, 31 (57%) were males and 23 (43%) were females.
This study enrolled people if they had:
• Newly diagnosed AML that was untreated or not suited for chemotherapy (unfit)
• R/R AML
The study was planned to enroll people with AML who were cancer-free for a while but still had small traces of the disease, also called MRD positive (MRD+) to test magrolimab with CC-486. However, this group did not enroll participants as not enough people with the required criteria were found.
What happened during the study?
This was an open-label, Phase 2 study.
• Open label means the participant and the study doctor/study staff knew the treatments the participants were taking.
• Phase 2 means that researchers tested magrolimab combinations in a small number of people with AML.
What treatments did participants take?
The study treatments were given as a slow injection into a vein (IV) in 28-day cycles. A cycle is the interval between the end of one treatment to the start of the next.
All participants took magrolimab based on their weight, starting at 1 mg/kg then 15 mg/kg, and then 30 mg/kg in combination with chemotherapy medicines, as mentioned below:
• Group 1 (Untreated, Unfit AML: Magrolimab + Venetoclax + Azacitidine): 18 participants. This group tested the combination of magrolimab + azacitidine 75 mg/m2 as an injection under the skin or IV + venetoclax 100 mg, then 200 mg, and then 400 mg as tablets by mouth.
• Group 2 (R/R AML: Magrolimab + MEC): 36 participants. This group tested magrolimab + MEC: Mitoxantrone 8 mg/m2 IV + Etoposide 100 mg/ m2 IV + Cytarabine 1000 mg/ m2 IV.
Group 1 participants took the treatment until the end of the study. Group 2 participants took it for a maximum of 12 months. The treatments were stopped if participants’ disease got worse, they had unacceptable side effects, they decided to leave the study, or they died.
What were the results of the study?
This is a summary of the main results from this study. No participants were enrolled in Group 3, so results are only available for Groups 1 and 2.
How many participants achieved CR or maintained CR with no disease (MRD- status)?
• Group 1 (Untreated, Unfit AML: Magrolimab + Venetoclax + Azacitidine): 7 out of 18 (39%) participants achieved CR
• Group 2 (R/R AML: Magrolimab + MEC): 9 out of 36 (25%) participants achieved CR
The researchers did not consider the results in Group 1 to be significant because not enough people joined the study. They could not make a proper comparison with other treatments.
In Group 2, even though the 25% of participants achieved CR (higher than the 19% in previous studies), the researchers still did not think the results were meaningful either.
How many participants had DLTs in the study, if any?
The researchers checked the safety and tolerability of various doses of magrolimab along with other chemotherapy medicines in 6 participants each in Group 1 and Group 2.
They found that none of the participants in any of the groups had any DLTs up to the highest dose of magrolimab (30 mg/kg).
How many participants had any unwanted medical events (TEAEs) and abnormalities in their laboratory test results during the study?
• Group 1 (Untreated, Unfit AML: Magrolimab + Venetoclax + Azacitidine): TEAEs and abnormalities in laboratory test results: All 18 (100%) participants
• Group 2 (R/R AML: Magrolimab + MEC): TEAEs: 35 of 36 (97%) participants; abnormalities in laboratory test results: All 35 (100%) participants
What side effects did participants have during the study?
Below is a summary of the side effects for all study participants.
Out of 54 participants, 46 (85%) had side effects, 22 (41%) had serious side effects, and 6 (11%) discontinued the study drug due to side effects.
A side effect is considered “serious” if i) results in death, ii) is life-threatening, iii) is considered by the study doctor to be medically important, iv) causes lasting problems v) requires hospital care, vi) causes a birth defect.
One death occurred in Group 1 (Untreated, Unfit AML: Magrolimab + Venetoclax + Azacitidine), due to a side effect of shortness of breath (dyspnoea).
The most common (top 3) serious side effects were:
- Fever with low number of white blood cells (febrile neutropenia)
- Inflammation in the body caused by a strong immune response to an infection (sepsis)
- Low number of white blood cells (neutropenia)
The most common (top 3) non-serious side effects were:
- Feeling sick to the stomach (nausea)
- Low number of red blood cells (anaemia)
- Low number of platelets (platelet count decreased)
The non-serious side effects were the side effects that were not serious in nature and did not meet the definition of ‘serious side effects’.
There were other serious and non-serious side effects, but those occurred in fewer participants. Some participants may have had more than 1 serious or non-serious side effect.
This summary was created and approved by Gilead Sciences in November 2024. The information in this summary does not include any information available after this date.
Thank you!REC name
Wales REC 1
REC reference
21/WA/0315
Date of REC Opinion
15 Nov 2021
REC opinion
Further Information Favourable Opinion