Ph1b Hu5F9G4Mono or Hu5F9G4&Azacitidine for hematological Malignancies
Research type
Research Study
Full title
A Phase 1b Trial of Hu5F9-G4 Monotherapy or Hu5F9-G4 in Combination with Azacitidine in Patients with Hematological Malignancies
IRAS ID
229775
Contact name
Paresh Vyas
Contact email
Sponsor organisation
Forty Seven Inc
Eudract number
2017-000678-12
Duration of Study in the UK
1 years, 8 months, 0 days
Research summary
Research Summary:
The purpose of this study is to test the safety of Hu5F9-G4 in patients with blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).In addition, it will also be used to determine the best dose of Hu5F9-G4, the side effects patients may experience, the quantity of Hu5F9-G4 present in patient's blood and whether it improves patient's cancer.This trial is an open label, multicentre, Phase 1b trial investigating monothearpy in patients with relapsed an/or refractory AML or intermediate/high/very high risk MDS and Hu5F9-G4 in combination with azacitidine in newly diagnosed AML patients ineligible for standard induction chemotherapy and newly diagnosed intermediated/high/very high risk MDS patients. There will be 3 cohorts of patients in this study;
Relapsed/Refractory (R/R) Cohort: for patient's whose blood cancer has come back after standard treatment, has not responded to standard treatment or cannot tolerate conventional cancer treatments
Treatment Naive/Unfit (TN/U) Cohort: for patient's who have not received or might be unsuitable (unfit) to receive prior anti cancer treatment for their blood cancer.
Rollover Cohort: for patient's who were previously enrolled in another trial that was studying Hu5F9-G4This study is open to male or female patients who are 18 years or older and who meet the criteria for one of the above cohorts along with all other inclusion criteria.
Patients will continue on this study until their disease progresses, they have loss of clinical benefit or they discontinue due to unacceptable drug-related toxicity.
Summary of Results:
The purpose of this study was to find out if magrolimab, given alone or in combination with azacitidine, was safe, tolerable, and effective for treating blood cancers, also called hematological malignancies.
Magrolimab, also known as Hu5F9-G4 or 5F9, is an investigational drug. In this study, it was tested to treat people with blood cancers, myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Azacitidine is a common drug used by doctors to treat people with MDS or AML.
What are MDS and AML?
In healthy people, bone marrow makes 3 types of blood cells: red blood cells (RBCs), white blood cells (WBCs), and platelets. In MDS, the marrow becomes faulty and starts making defective or immature blood cells. This leads to problems like anemia (low RBCs), infections (due to low WBCs), and bleeding (due to low platelets). Some people with MDS need blood transfer to manage their condition. This means they have to take the blood from other healthy people. MDS is often classified into different risk levels, from very low-risk to very high-risk, based on certain factors. AML is a type of blood cancer where the marrow makes too many defective or immature blood cells. If left untreated, people with AML may die.
People with MDS or AML joined the study in specific groups, based on the following criteria:
a) Treatment-naive or unfit (TN/U): People who recently found out that they have higher-risk (HR) MDS and did not take any treatment for it. People with intermediate-, high- or very high-risk MDS were grouped together as HR MDS. People with AML who did not take or were unfit for available treatments.
b) Relapsed or refractory (r/r) MDS or AML: People with MDS or AML whose disease kept coming back (relapsed) or were not responding to the available treatments (refractory).
c) Rollover: Participants from another AML study who were already taking magrolimab.
d) People with low-risk MDS, needing regular blood transfer.
The main questions the researchers wanted to answer in this study were:
• How many participants had treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the study, if any?
• How many participants responded to treatment and achieved complete remission?
• How many low-risk MDS participants stayed free from blood transfer for at least 8 continuous weeks?
• What side effects did participants have during the study, if any?
The researchers assessed the safety of study treatments in participants by monitoring all “AEs”. They also monitored if those AEs were related to the study treatments, called as “side effects”. The AEs are unwanted medical events that occurred during the study, which may or may not be related to the study treatment. An AE is considered “serious” if it leads to death, is life-threatening, considered by the study doctor to be medically important, causes lasting problems, or, requires inpatient hospital care. TEAEs were those that started or got worse after initiating the treatment.
Complete remission means participants had improvement in their disease. Their tests showed a rise in healthy blood cells and reduction of defective or immature blood cells in the bone marrow or their absence in the blood stream.
What happened in the study?
The study began in September 2017 and ended in September 2023. Sponsor stopped the study earlier than planned, however, the researchers did not expect any significant impact of stopping the study earlier on the study results. This was because by the time the study was stopped, most of the MDS and AML participants already completed the treatment.
The researchers stopped the study based on the findings from another similar magrolimab + azacitidine Gilead study. In that study, magrolimab + azacitidine treatment did not show expected results in people with MDS, and there were safety concerns.
This was an open¬ label study. Open label means, the participant and the study doctor/study staff knew the treatments the participants were taking. A total of 258 participants from the United Kingdom and the United States took part.
Below is the participants break-down by each group and the treatments they took:
TN/U groups (all took magrolimab + azacitidine):
• 96 TN/U MDS participants, which included 95 HR MDS participants and 1 low-risk MDS participant, who got enrolled accidentally in this group.
• 87 TN/U AML participants.
r/r AML groups:
• 19 participants took magrolimab + azacitidine.
• 6 participants took magrolimab alone.
• 1 rollover participant who continued with magrolimab alone.
r/r MDS groups:
• 17 participants took magrolimab + azacitidine.
• 5 participants switched from magrolimab to magrolimab + azacitidine.
• 10 participants took magrolimab alone.
Low-risk MDS groups, needing regular blood transfer:
• 9 participants took magrolimab + azacitidine.
• 5 participants switched from magrolimab to magrolimab + azacitidine.
• 3 participants took magrolimab alone.
Magrolimab was given as a slow injection into a vein, starting at a low dose of 1 mg/kg. Doses (mg/kg) of magrolimab were based on participant’s weight. The dose was gradually increased to 30 or 60 mg/kg, given once or two times a week, in a 28-day cycle. Azacitidine was given at a fixed dose of 75 mg/m2 as a slow injection into a vein or an injection under the skin, for 7 days in a 28-day cycle. Participants took the treatment until they continued to get benefit from it. The treatment was stopped if their symptoms showed worsening, they had unacceptable side effects, they decided to leave study, or they died. All participants have got off-study.
What were the results of the study?
This is a summary of the main results from this study. To find out the safety of the study treatments, the researchers tracked TEAEs the participants had during the study.
The below summary shows participants who had TEAEs and SAEs in each group:
• TN/U groups: 94 of 96 (98%) MDS participants had TEAEs, and 60 of 96 (63%) participants had SAEs. All 87 (100%) AML participants had TEAEs, and 64 of 87 (74%) participants had SAEs.
• r/r AML groups: All participants had TEAEs. 17 of 19 (90%) participants who took magrolimab + azacitidine had SAEs. Of those who took magrolimab alone, 4 of 6 (67%) participants, along with the one rollover participant had SAEs.
• r/r MDS groups: All participants had TEAEs. 12 of 17 (71%) participants who took magrolimab + azacitidine and 2 of 5 (40%) participants who switched to magrolimab + azacitidine had SAEs. of those who took magrolimab alone, 7 of 10 (70%) had SAEs.
• Low-risk MDS groups, needing regular blood transfer: All participants had TEAEs. 8 of 9 (89%) participants who took magrolimab + azacitidine and 3 of 5 (60%) participants who switched to magrolimab + azacitidine had SAEs. Of those who took magrolimab alone, only 1 of 3 (33%) participant had an SAE.
To find the effectiveness of the study treatments, the researchers checked how many participants achieved CR. They also checked how many low risk MDS participants stayed free from blood transfer for at least 8 continuous weeks. This was assessed in participants who depended on regular blood transfer, at the beginning of the study.
The below summary shows:
a) Participants who achieved CR:
• TN/U groups: 31 of 95 (33%) among higher-risk MDS participants achieved CR. 28 of 87 (32%) AML participants achieved CR.
• r/r AML, r/r MDS and the low-risk MDS groups: None of the participants achieved CR, except the 1 of 9 (11%) participants with low-risk MDS who took magrolimab + azacitidine.
b) Low-risk MDS participants who stayed free from blood transfer for at lest 8 continuous weeks included:
• 3 of 8 (38%) participants who took magrolimab + azacitidine
• 2 of 5 (40%) of those who switched to magrolimab + azacitidine
• However, none of the 3 participants who took magrolimab alone, stayed free from blood transfer for at least 8 continuous weeks.
What did researchers find about the safety of magrolimab both alone and combined with azacitidine?
Beside the TEAEs, the researchers monitored the “side effects” the participants had during the study. Almost all participants had some side effects during the study.
The below summary shows participants with “serious” side effects in each group:
• TN/U groups: 29 of 96 (30%) MDS participants and 25 of 87 (29%) AML participants had serious side effects.
• r/r AML groups: 3 of 19 (16%) participants who took magrolimab + azacitidine had serious side effects. None of the participants in other AML groups had any serious side effects.
• r/r MDS groups: 5 of 17 (29%) participants who took magrolimab + azacitidine treatment and 1 of 5 (20%) of those who switched to magrolimab + azacitidine had serious side effects. For those who took magrolimab alone, 3 of 10 (30%) participants had serious side effects.
• Low-risk MDS groups, needing regular blood transfer: 4 of 9 (44%) participants who took magrolimab + azacitidine had serious side effects. None of the participants in other low-risk MDS groups had any serious side effects.
The most common (top 3) serious side effects were febrile neutropenia (fever with low number of white blood cells), infusion-related reaction (reaction during or following infusion of a drug), and anemia. There were 4 deaths noted due to side effects in 1 participant each in TN/U MDS, r/r AML, r/r MDS, and low-risk MDS groups, taking magrolimab + azacitidine.REC name
South Central - Oxford B Research Ethics Committee
REC reference
17/SC/0450
Date of REC Opinion
13 Nov 2017
REC opinion
Further Information Favourable Opinion