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A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve (COMMANDS)

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ClinicalTrials.gov Identifier: NCT03682536
Recruitment Status : Recruiting
First Posted : September 24, 2018
Last Update Posted : July 18, 2022
Sponsor:
Collaborator:
Acceleron Pharma Inc.
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE September 7, 2018
First Posted Date  ICMJE September 24, 2018
Last Update Posted Date July 18, 2022
Actual Study Start Date  ICMJE January 2, 2019
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2022)
Red blood cell transfusion independence (RBC-TI) for 12 weeks (84 days) with a mean hemoglobin increase ≥ 1.5 g/dL [ Time Frame: Week 1 through Week 24 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 20, 2018)
Red Blood Cell Transfusion Independence (RBCTI) for 24 weeks [ Time Frame: Randomization through Week 24 ]
Proportion of subjects who are RBC transfusion free over the first 24 weeks from randomization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2022)
  • RBC-TI for 24 weeks [ Time Frame: Week 1 through Week 24 ]
  • Mean hemoglobin change over 24 weeks [ Time Frame: Week 1 through Week 24 ]
  • Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG) [ Time Frame: Week 1 through Week 24 ]
  • Time to HI-E [ Time Frame: Week 1 through Week 24 ]
  • RBC-TI for ≥ 12 weeks (84 days) [ Time Frame: Week 1 through Week 24 ]
  • Duration of RBC-TI ≥ 12 weeks (84 days) [ Time Frame: Week 1 through End of Treatment (EOT), up to approximately 60 months ]
  • Time to RBC-TI ≥ 12 weeks (84 days) [ Time Frame: Week 1 through Week 24 ]
  • Time to first red blood cell (RBC) transfusion [ Time Frame: Week 1 through EOT, up to approximately 60 months ]
  • RBC transfusion burden on treatment [ Time Frame: Week 1 through Week 24 ]
  • RBC-TI for ≥ 56 days (8 weeks) [ Time Frame: Week 1 through Week 24 ]
  • RBC-TI for a consecutive 24-week period [ Time Frame: Week 1 through Week 48 ]
  • The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) [ Time Frame: Screening through Week 24 ]
  • The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire [ Time Frame: Screening through Week 24 ]
  • Number of participants with Adverse Events (AEs) [ Time Frame: Week 1 through 42 days post last dose ]
  • Pharmacokinetic - area under the concentration-time curve (AUC) [ Time Frame: Randomization through 1-year post first dose ]
  • Pharmacokinetic - maximum plasma concentration of drug (Cmax) [ Time Frame: Randomization through 1-year post first dose ]
  • Frequency of antidrug antibodies (ADA) [ Time Frame: Randomization through 1-year post first dose ]
  • Number of participants progressing to acute myeloid leukemia (AML) [ Time Frame: Randomization through up to 60 months ]
  • Percentage of participants progressing to AML [ Time Frame: Randomization through up to 60 months ]
  • Time to AML progression [ Time Frame: Randomization through up to 60 months ]
  • Overall survival [ Time Frame: Randomization through up to 60 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2018)
  • Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG) within 24 weeks [ Time Frame: Randomization through Week 24 ]
    Proportion of subjects achieving HI-E over any consecutive 56-day period
  • Mean hemoglobin increase ≥ 1.5 g/dL [ Time Frame: Randomization through Week 24 ]
    Proportion of subjects achieving ≥ 1.5 g/dL mean increase in hemoglobin over the first 24 weeks from randomization compared to baseline in the absence of RBC transfusions
  • Time to Hematologic improvement - erythroid response (HI-E) [ Time Frame: Randomization through Week 48 ]
    Time from first dose to first onset of achieving ≥ 1.5 g/dL increase in hemoglobin over any consecutive 56-day period in the absence of RBC transfusions
  • Duration of HI-E [ Time Frame: Randomization through Week 48 ]
    Maximum duration of achieving ≥ 1.5 g/dL increase in hemoglobin for subjects who achieve mean hemoglobin increase ≥ 56 days in the absence of RBC transfusions
  • Duration of Red blood cell transfusion independence (RBC-TI) ≥ 24 weeks [ Time Frame: Randomization through Week 48 ]
    Maximum duration of RBC transfusion independence for subjects who achieve RBC TI ≥ 24 weeks
  • RBC-TI for ≥ 84 days [ Time Frame: Randomization through Week 24 ]
    Proportion of subjects who are RBC transfusion free over a consecutive 84-day period
  • Duration of RBC-TI ≥ 84 days [ Time Frame: Randomization through Week 48 ]
    Maximum duration of RBC transfusion independence for subjects who achieve RBC TI ≥ 84 days
  • Time to RBC-TI ≥ 84 days [ Time Frame: Randomization through Week 24 ]
    Time from randomization to first onset of transfusion independence ≥ 84 days
  • Time to first Red blood cell (RBC) transfusion [ Time Frame: Randomization through Week 48 ]
    Time from randomization to first transfusion on treatment
  • RBC transfusion burden on treatment [ Time Frame: Randomization through Week 24 ]
    Total number of RBC units transfused on treatment
  • For subjects with RBC transfusion burden of ≥4 units/8 weeks at baseline: [ Time Frame: Randomization through Week 48 ]
    Mean change in total Packed red blood cells (pRBC) units transfused over a rolling 8-week period
  • RBC-TI during Weeks 4-24 [ Time Frame: Week 4 through Week 24 ]
    Proportion of subjects who are RBC transfusion independent during Weeks 4-24
  • RBC-TI for a consecutive 24-week period [ Time Frame: Randomization through Week 48 ]
    Proportion of subjects who are RBC transfusion free for a consecutive 24-week period in the first 48 weeks from Randomization
  • The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) [ Time Frame: Screening through Week 48 ]
    Is a validated HRQoL measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning.
  • The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire [ Time Frame: Screening through Week 48 ]
    Is a validated instrument specific in measuring HRQoL related anemia. The 47-item FACT-An scale measures cancer-related symptoms with 13 items that measure fatigue (the FACIT-Fatigue subscale) and an additional 7 items that measure items pertinent to anemia.
  • Adverse Event (AE) [ Time Frame: Randomization through Week 48 ]
    Type, frequency, severity of AEs and relationship of AEs to luspatercept/epoetin alfa
  • Pharmacokinetic - AUC [ Time Frame: Randomization through 1-year post first dose. ]
    Area under the concentration-time curve
  • Pharmacokinetic - Cmax [ Time Frame: Randomization through 1-year post first dose. ]
    Maximum plasma concentration of drug
  • Antidrug antibodies (ADA) [ Time Frame: Randomization through 1-year post first dose. ]
    Frequency of antidrug antibodies and effects on efficacy, safety or PK
  • Progression to AML [ Time Frame: Randomization through at least 5 years post last dose ]
    Number and percentage of subjects progressing to AML
  • Time to AML [ Time Frame: Randomization through at least 5 years post last dose ]
    Time between randomization and first diagnosis of AML
  • Overall survival [ Time Frame: Randomization through at least 5 years post last dose; ]
    Time from date of randomization to death due to any cause
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve
Official Title  ICMJE A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) ESA in Native Subjects Who Require Red Blood Cell Transfusions
Brief Summary The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: Luspatercept
    Specified dose on specified days
    Other Name: ACE-536
  • Drug: Epoetin alfa
    Specified dose on specified days
    Other Names:
    • EPREX®
    • ERYPO®
    • PROCRIT®
Study Arms  ICMJE
  • Experimental: Luspatercept
    Intervention: Drug: Luspatercept
  • Active Comparator: Epoetin alfa
    Intervention: Drug: Epoetin alfa
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: September 20, 2018)
350
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2027
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented diagnosis of Myelodysplastic syndromes (MDS) according to WHO 2016 classification that meets revised international prognostic scoring system (IPSS-R) classification of very low, low, or intermediate risk disease, and have < 5% blasts in bone marrow
  • Endogenous serum erythropoietin (sEPO) level of < 500 U/L
  • Requires Red blood cell (RBC) transfusions, as documented by the criteria: Average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells (pRBCs) confirmed for a minimum of 8 weeks immediately preceding randomization
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

Exclusion Criteria:

  • Clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any type of known clinically significant bleeding or sequestration or drug induced anemia
  • Known history of diagnosis of Acute myeloid leukemia (AML)
  • Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment

Other protocol-defined inclusion/exclusion criteria 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: BMS Study Connect Contact www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Contact: First line of the email MUST contain the NCT# and Site #.
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Netherlands,   Poland,   Portugal,   Russian Federation,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03682536
Other Study ID Numbers  ICMJE ACE-536-MDS-002
U1111-1218-1810 ( Registry Identifier: WHO )
2017-003190-34 ( 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 Not Provided
Current Responsible Party Celgene
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Celgene
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Acceleron Pharma Inc.
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Celgene
Verification Date July 2022

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