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

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ClinicalTrials.gov Identifier: NCT04313881
Recruitment Status : Recruiting
First Posted : March 18, 2020
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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 duration of CR.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Magrolimab Drug: Azacitidine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 9, 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : October 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Azacitidine

Arm Intervention/treatment
Experimental: Magrolimab + Azacitidine

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

Drug: Magrolimab
Administered intravenously
Other Name: Hu5F9-G4

Drug: Azacitidine
Administered either subcutaneously (SB) or intravenously (IV) according to region-specific drug labeling

Placebo Comparator: Control Arm (Placebo + Azacitidine)

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

Drug: Azacitidine
Administered either subcutaneously (SB) or intravenously (IV) according to region-specific drug labeling

Drug: Placebo
Placebo to match magrolimab administered intravenously




Primary Outcome Measures :
  1. Proportion of Participants with Complete Remission (CR) [ Time Frame: Up to 19 months ]
    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.

  2. Duration of CR [ Time Frame: Up to 5 years ]
    The duration of CR is measured from the time measurement criteria are first met for CR to the first date of relapse.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the length measured from randomization to the date of death from any cause.

  2. Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
    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.

  3. Duration of Response (DOR) [ Time Frame: Up to 5 years ]
    DOR is measured from the time measurement criteria are first met for objective response to the first date of relapse.

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

  5. Duration of RBC Transfusion Independence [ Time Frame: Up to 5 years ]
    The duration of RBC transfusion independence is measured from the date on which measurement criteria are first met for RBC transfusion independence to the first date of RBC transfusion prior to initiation of any new MDS therapy.

  6. Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
    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.

  7. Event Free Survival (EFS) [ Time Frame: Up to 5 years ]
    The length of EFS is defined as the time from randomization to the date of documented treatment failure (defined as treatment discontinuation without an objective response per IWG 2006 MDS criteria [Cheson 2003]), disease progression, relapse, or death from any cause, whichever occurs first.

  8. Relapse-free Survival (RFS) [ Time Frame: Up to 5 years ]
    The length of RFS is defined as the time from the date on which measurement criteria are first met for CR to the date of documented relapse or death for participants who achieve a CR.

  9. Minimal Residual Disease (MRD)-negative Response Rate [ Time Frame: Up to 5 years ]
    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.

  10. Time to Transformation to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 5 years ]
    Time to transformation to AML is defined as the time from randomization to the date of documented AML diagnosis.

  11. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 5 years ]
  12. 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 ]
  13. 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 ]
  14. Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate [ Time Frame: Up to 5 years ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein
  • alpha (SIRPα)-targeting agents
  • Any prior antileukemic therapy
  • 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.
  • Pregnancy or active breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04313881


Contacts
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Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations
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United States, Alabama
University of Alabama Birmingham Recruiting
Birmingham, Alabama, United States, 35294
United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
UCLA Ronald Reagan Medical Center Recruiting
Los Angeles, California, United States, 90095
UC Irvine Health Recruiting
Orange, California, United States, 92868
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
University of Maryland, Greenebaum Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
United States, Missouri
Mid America Division, Inc. Recruiting
Kansas City, Missouri, United States, 64132
Washington University School of Medicine - Siteman Cancer Center Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center - Herbert Irving Pavilion Recruiting
New York, New York, United States, 10032
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
Prisma Health Cancer Center Recruiting
Greenville, South Carolina, United States, 29615
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04313881    
Other Study ID Numbers: 5F9009
2020-004287-26 ( EudraCT Number )
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Hu5F9-G4
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antineoplastic Agents, Immunological