Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 11, 2020
First Posted Date  ICMJE March 18, 2020
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE September 9, 2020
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
CR rate and duration of CR [ Time Frame: 6 months after last patient randomized ]
To evaluate the efficacy of magrolimab + azacitidine, compared to that of azacitidine + placebo, in previously untreated patients with intermediate/high/very high risk MDS by IPSS-R as measured by CR and duration of CR
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 5 years ]
  • 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 ]
  • 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 ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Overall Survival [ Time Frame: Through Study Completion, up to 4 years after the last patient is randomized. ]
    To evaluate the survival benefit of magrolimab + azacitidine compared to azacitidine + placebo
  • ORR [ Time Frame: From Start of treatment until disease progression/recurrence, up to 4 years after the last patient is randomized. ]
    To evaluate the objective response rate (ORR) of magrolimab + azacitidine compared to that of azacitidine + placebo
  • DOR [ Time Frame: From Start of treatment until disease progression/recurrence, up to 4 years after the last patient is randomized. ]
    To evaluate the duration of response (DOR) of magrolimab + azacitidine compared to that of azacitidine + placebo
  • Red Blood Cell (RBC) Transfusion Independence Rate [ Time Frame: Any time between randomization and initiation of any new MDS therapy among all patients who are RBC transfusion-dependent at Baseline, assessed up to 4 years after the last patient is randomized. ]
    Proportion of patients who have a 56-day or longer period with no RBC transfusions
  • Duration of RBC Transfusion Independence [ Time Frame: 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, assessed up to 4 years after the last patient is randomized. ]
    To evaluate duration of RBC transfusion independence of magrolimab + azacitidine compared to that of azacitidine + placebo
  • Progression Free Survival (PFS) [ Time Frame: From Randomization to the date of documented disease progression, relapse, or death from any cause. This can be assessed up to 4 years after the last patient is randomized. ]
    To evaluate the efficacy of magrolimab + azacitidine, compared to that of azacitidine + placebo, as measured by PFS
  • Event Free Survival (EFS) [ Time Frame: From Randomization tot he date of documented treatment failure, disease progression, relapse, or death from any cause. This can be assessed up to 4 years after the last patient is randomized. ]
    To evaluate the efficacy of magrolimab + azacitidine compared to that of azacitidine + placebo as measured by EFS
  • Relapse-free Survival (RFS) [ Time Frame: From the date on which measurement criteria are first met for CR to date of documented relapse or death for patients who achieve CR. This can be assessed up to 4 years after the last patient is randomized. ]
    To evaluate RFS of magrolimab + azacitidine compared to that of azacitidine + placebo
  • Minimal Residual Disease (MRD)-negative Response Rate [ Time Frame: Prior to initiation of any new MDS therapy ]
    the proportion of patients who achieve a morphologic CR or marrow CR based on Investigator-assessed International Working Group (IWG) criteria and reach MRD-negative disease status
  • Time to Transformation to Acute Myeloid Leukemia (AML) [ Time Frame: From Randomization to date of documented AML diagnosis. This can be measured up to 4 years after the last patient is randomized ]
    To assess time to transformation to AML of magrolimab + azacitidine compared to that of azacitidine + placebo
  • Measurement of AEs [ Time Frame: Adverse events will be collected beginning at screening and then at all subsequent time points. This can be assessed up to 4 years after the last patient is randomized. ]
    This will be measured in accordance to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.00
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: Magrolimab
    Administered intravenously
    Other Name: Hu5F9-G4
  • Drug: Azacitidine
    Administered either subcutaneously (SB) or intravenously (IV) according to region-specific drug labeling
  • Drug: Placebo
    Placebo to match magrolimab administered intravenously
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: Magrolimab
    • Drug: Azacitidine
  • 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

    Interventions:
    • Drug: Azacitidine
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 17, 2020)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2025
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04313881
Other Study ID Numbers  ICMJE 5F9009
2020-004287-26 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP