Brief Summary
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).
Brief Title
Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Myelodysplastic Syndromes
Eligibility Criteria
Key Inclusion Criteria:
* Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
* Adequate performance status and hematological, liver, and kidney function.
Key Exclusion Criteria:
* Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor.
* Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
* Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R.
* Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year.
* Contraindications to azacitidine.
* Clinical suspicion of active central nervous system (CNS) involvement by MDS.
* Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history .
* Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening.
* Pregnancy or active breastfeeding.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
* Adequate performance status and hematological, liver, and kidney function.
Key Exclusion Criteria:
* Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor.
* Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
* Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R.
* Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year.
* Contraindications to azacitidine.
* Clinical suspicion of active central nervous system (CNS) involvement by MDS.
* Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history .
* Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening.
* Pregnancy or active breastfeeding.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
* Adequate performance status and hematological, liver, and kidney function.
Inclusion/
* Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
* Adequate performance status and hematological, liver, and kidney function.
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04313881
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
5F9009
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With Complete Remission (CR)
Outcome Time Frame
From randomization up to 31.01 months
Outcome Description
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.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
From randomization up to 32.62 months
Secondary Ids
Secondary Id
2020-004287-26
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Duration of CR (DOCR)
Outcome Description
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.
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.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Objective Response Rate (ORR)
Outcome Description
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.
Disease progression and relapse have been defined in outcome measure number 3. KM estimates were used for analysis.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
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.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Red Blood Cell (RBC) Transfusion Independence Rate
Outcome Description
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
Transformation assessments and deaths post SCT were included in the analysis. KM estimates were used for analysis
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Event Free Survival (EFS)
Outcome Description
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.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Percentage of Participants With CR in Participants With TP53 Mutation
Outcome Description
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.
Morphologic CR and marrow CR are defined in outcome measures 1 and 4, respectively.
Percentages were rounded off.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Minimal Residual Disease (MRD)-Negative Response Rate
Outcome Description
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.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Time to Transformation to AML
Outcome Description
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.
CR, PR and PD are defined in outcome measures 1, 4 and 5 respectively. KM estimates were used for analysis.
Outcome Time Frame
From randomization up to 31.01 months
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
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.
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.
Outcome Time Frame
Up to week 136
Outcome Measure
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate
Outcome Description
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.
Outcome Time Frame
First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)
Outcome Measure
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
Outcome Description
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.
Outcome Time Frame
Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336
Outcome Measure
Serum Concentration of Magrolimab
Outcome Description
Percentages were rounded off.
Outcome 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
Outcome Measure
Percentage of Participants With Positive Anti-magrolimab Antibodies
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900