The primary objective of this study is to evaluate the efficacy of magrolimab in combination with azacitidine compared to that of azacitidine plus placebo in previously untreated participants with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R) as measured by complete remission (CR) and overall survival (OS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
539
Administered intravenously
Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling
Placebo to match magrolimab administered intravenously
Percentage of Participants With Complete Remission (CR)
The percentage of participants (CR rate) are participants who reach morphologic CR (morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast) based on Investigator-assessed International Working Group (IWG) myelodysplastic syndrome (MDS) criteria on or prior to initiation of any new anticancer therapy, including stem cell therapy (SCT). Percentages were rounded off.
Time frame: From randomization up to 31.01 months
Overall Survival (OS)
OS is defined as the number of months measured from the date of randomization to the date of death from any cause. Kaplan Meier (KM) estimates were used for analysis.
Time frame: From randomization up to 32.62 months
Duration of CR (DOCR)
DOCR=Time from first CR date to the first date of relapse, disease progression (PD) or death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. PD is defined as: \<5% blasts: ≥50 increase in blasts to \>5% blasts,5%-10% blasts: ≥50% increase in blasts to \>10% blasts, 10%-20% blasts: ≥50% increase in blasts to \>20% blasts,20%-30% blasts: ≥50% increase in blasts to \>30% blasts, any of the following: at least 50% decrement from maximum remission/response in granulocytes or platelets. Reduction in Hgb by ≥2 g/dL / Transfusion dependence. Relapse is defined as return to pretreatment bone marrow blast percentage / decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets/ reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR is defined in outcome measure 1. KM estimates were used for analysis.
Time frame: From randomization up to 31.01 months
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who reach objective response including CR, partial remission (PR), marrow CR or hematological improvement prior to initiation of any new anticancer therapy including SCT for MDS per IWG 2006 criteria per investigator's evaluation. CR is defined in outcome measure 1. PR is defined as all CR criteria if abnormal before treatment except, one marrow blasts decreased by ≥ 50% over pretreatment but still \> 5% cellularity and morphology not relevant. Marrow CR is defined as bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment, stable disease with any hematological improvement, peripheral blood: if hematological improvement responses, they were noted in addition to marrow CR. Stable Disease: Failure to achieve at least PR, but no evidence of progression for \> 8 weeks. Percentages were rounded off.
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University of Alabama Birmingham
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences IRB
Little Rock, Arkansas, United States
City of Hope
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
UCLA Ronald Reagan Medical Center
Los Angeles, California, United States
UC Irvine Health
Orange, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of California, Davis Comprehensive Cancer Center
Sacramento, California, United States
University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
...and 159 more locations
Time frame: From randomization up to 31.01 months
Duration of Response (DOR)
DOR is measured from time measurement criteria are first met for objective response to first date of relapse, disease progression (PD) /death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. Disease progression and relapse have been defined in outcome measure number 3. KM estimates were used for analysis.
Time frame: From randomization up to 31.01 months
Red Blood Cell (RBC) Transfusion Independence Rate
RBC transfusion independence rate is defined as the percentage of participants who have a 56-day or longer period with no RBC transfusions at any time between randomization and initiation of any new anticancer therapy, including SCT, among all participants who were RBC transfusion-dependent at Baseline. Percentages were rounded off.
Time frame: From randomization up to 31.01 months
Event Free Survival (EFS)
EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first. Transformation assessments and deaths post SCT were included in the analysis. KM estimates were used for analysis
Time frame: From randomization up to 31.01 months
Percentage of Participants With CR in Participants With TP53 Mutation
CR in TP53 mutant population is defined as the percentage of participants who achieve a morphologic CR based on investigator assessments using IWG criteria on or prior to initiation of any new anticancer therapy, including SCT in TP53 mutant population. Percentages were rounded off.
Time frame: From randomization up to 31.01 months
Minimal Residual Disease (MRD)-Negative Response Rate
The MRD-negative response rate is defined as the percentage of participants who achieved a morphologic CR or marrow CR based on Investigator-assessed IWG criteria and reached MRD-negative disease status prior to initiation of any new anticancer therapy, including SCT. MRD-negative disease status was assessed using a multiparameter flow cytometry-based assay performed by a central laboratory. Morphologic CR and marrow CR are defined in outcome measures 1 and 4, respectively. Percentages were rounded off.
Time frame: From randomization up to 31.01 months
Time to Transformation to AML
Time to transformation to AML is defined as the time from randomization to the collection date of bone marrow sample leading to documented AML diagnosis. Transformation assessments post SCT were included in the analysis.KM estimates were used for analysis.
Time frame: From randomization up to 31.01 months
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the date of documented DP (including treatment failure by IWG criteria or relapse after PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post SCT were included in the analysis. Treatment failure is defined as, Death during treatment or disease progression characterized by worsening cytopenia, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment. Relapse after CR or PR = Return to pretreatment bone marrow blast percentage / Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets / Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR, PR and PD are defined in outcome measures 1, 4 and 5 respectively. KM estimates were used for analysis.
Time frame: From randomization up to 31.01 months
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate
The FACT-Anemia response rate is defined as the percentage of participants who showed clinically meaningful improvement in health-related quality of life (HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new anticancer therapy, including SCT. The minimal clinically meaningful difference of 7.0 was used as cutoff for clinically meaningful improvement. The FACT-Anemia instrument consists of 5 subscales, including physical well-being, emotional well-being, functional well-being, social well-being, and anemia symptoms. Each subscale measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much. The subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest quality of life (QOL) and 100 denotes the highest QOL. Percentages were rounded off.
Time frame: Up to week 136
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
TEAE's are defined as any AEs with an onset date on or after the study drug start date, no later than 70 days after study drug last dose date or day before initiation of new anticancer therapy including SCT. If AE onset date is on or before last dose date, it is considered as TEAE regardless of start of new anticancer therapy. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product or other protocol imposed intervention, regardless of attribution. An event is considered "serious", if it results death, life-threatening, inpatient or prolongation hospitalization, incapacity or substantial disruption of the ability to conduct normal functions, a congenital anomaly/birth defect, and important medical events.
Time frame: First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)
Serum Concentration of Magrolimab
Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected within 24 hours prior to study treatment administration.
Time frame: Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336
Percentage of Participants With Positive Anti-magrolimab Antibodies
Percentages were rounded off.
Time frame: Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days