Clinical Trial: NCT04313881 - My Cancer Genome

NCT04313881

Description:

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).

Related Conditions:

Myelodysplastic Syndromes

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04313881

Trial Eligibility

Document

Title

Brief Title: Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
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

Clinical Trial IDs

ORG STUDY ID: 5F9009
SECONDARY ID: 2020-004287-26
NCT ID: NCT04313881

Conditions

Myelodysplastic Syndromes

Interventions

Drug	Synonyms	Arms
Magrolimab	Hu5F9-G4	Magrolimab + Azacitidine
Azacitidine		Control Arm (Placebo + Azacitidine)
Placebo		Control Arm (Placebo + Azacitidine)

Purpose

Trial Arms

Name	Type	Description	Interventions
Magrolimab + Azacitidine	Experimental	Participants will receive the following magrolimab and azacitidine dosing regimens: Magrolimab: Cycle 1: 1mg/kg priming dose on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, and 22 Cycle 2: weekly doses of 30 mg/kg on Days 1, 8, 15, and 22 Cycle 3 and onward: 30 mg/kg every 2 weeks on Days 1 and 15 Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle	Magrolimab Azacitidine
Control Arm (Placebo + Azacitidine)	Placebo Comparator	Participants will receive the following placebo and azacitidine dosing regimens: Placebo: Cycle 1: Days 1, 4, 8, 11, 15, and 22 Cycle 2: Days 1, 8, 15, and 22 Cycle 3 and onward: Days 1 and 15 Azacitidine: 75 mg/m^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle	Azacitidine Placebo

Eligibility Criteria

        Key Inclusion Criteria:

          -  Previously untreated individuals with intermediate to very high risk Myelodysplastic
             Syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R)

          -  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

          -  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.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Proportion of Participants with Complete Remission (CR)
Time Frame:	Up to 24 months
Safety Issue:
Description:	The CR rate is the proportion of participants who reach morphologic CR based on Investigator-assessed International Working Group (IWG) 2006 Myelodysplastic Syndrome (MDS) criteria (Cheson 2006) prior to initiation of any new MDS therapy.

Secondary Outcome Measures

Measure:	Duration of CR
Time Frame:	Up to 5 years
Safety Issue:
Description:	The duration of CR is measured from the time measurement criteria are first met for CR to the first date of relapse or death, whichever occurs earlier.

Measure:	Objective Response Rate (ORR)
Time Frame:	Up to 5 years
Safety Issue:
Description:	ORR is defined as the proportion of participants who reach objective response including CR, complete remission with partial hematologic recovery (CRh), Partial Remission (PR), marrow CR, or hematologic improvement per IWG 2006 MDS criteria (with the addition of CRh) prior to initiation of any new MDS therapy.

Measure:	Duration of Response (DOR)
Time Frame:	Up to 5 years
Safety Issue:
Description:	DOR is measured from the time measurement criteria are first met for objective response to the first date of relapse or death, whichever occurs earlier.

Measure:	Red Blood Cell (RBC) Transfusion Independence Rate
Time Frame:	Up to 5 years
Safety Issue:
Description:	The RBC transfusion independence rate is the proportion of participants who have a 56-day or longer period with no RBC transfusions.

Measure:	Progression Free Survival (PFS)
Time Frame:	Up to 5 years
Safety Issue:
Description:	The length of PFS is defined as the time from randomization to the date of documented disease progression, relapse, or death from any cause, whichever occurs first.

Measure:	Event Free Survival (EFS)
Time Frame:	Up to 5 years
Safety Issue:
Description:	The length of EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first.

Measure:	Minimal Residual Disease (MRD)-negative Response Rate
Time Frame:	Up to 5 years
Safety Issue:
Description:	The MRD-negative response rate is defined as the proportion of participants who achieve a morphologic CR or marrow CR based on Investigator-assessed IWG criteria (Cheson 2006) and reach MRD-negative disease status prior to initiation of any new MDS therapy.

Measure:	Time to Transformation to Acute Myeloid Leukemia (AML)
Time Frame:	Up to 5 years
Safety Issue:
Description:	Time to transformation to AML is defined as the time from randomization to the date of documented AML diagnosis.

Measure:	Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:	Up to 5 years
Safety Issue:
Description:

Measure:	Serum Concentration of Magrolimab
Time Frame:	Up to 12 hours before administration of any treatment at Days 1 and 8 of Cycle1; 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
Safety Issue:
Description:

Measure:	Anti-magrolimab Antibody Positivity Occurrence Rate
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
Safety Issue:
Description:

Measure:	Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate
Time Frame:	Up to 5 years
Safety Issue:
Description:	The FACT-Anemia response rate is defined as the proportion 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 MDS therapy. 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.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Gilead Sciences

Last Updated

August 23, 2021

Clinical Trials /

Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)