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 :
Active, not recruiting
First Posted : September 24, 2018
Last Update Posted : December 1, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Myelodysplastic Syndromes | Drug: Luspatercept Drug: Epoetin alfa | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 363 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | January 2, 2019 |
Actual Primary Completion Date : | March 31, 2023 |
Estimated Study Completion Date : | September 28, 2027 |
Arm | Intervention/treatment |
---|---|
Experimental: Luspatercept |
Drug: Luspatercept
Specified dose on specified days
Other Name: ACE-536 |
Active Comparator: Epoetin alfa |
Drug: Epoetin alfa
Specified dose on specified days
Other Names:
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- 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 ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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): NCT03682536
Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Responsible Party: | Celgene |
ClinicalTrials.gov Identifier: | NCT03682536 |
Other Study ID Numbers: |
ACE-536-MDS-002 U1111-1218-1810 ( Registry Identifier: WHO ) 2022-501485-22-00 ( Other Identifier: EU CTR ) |
First Posted: | September 24, 2018 Key Record Dates |
Last Update Posted: | December 1, 2023 |
Last Verified: | November 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Luspatercept ACE-536 Anemia Myelodysplastic Syndromes Blood Transfusion |
RBC Transfusion Erythropoiesis-stimulating agents Erythropoietin Myelodysplasia |
Preleukemia Anemia Myelodysplastic Syndromes Syndrome Disease Pathologic Processes Hematologic Diseases |
Bone Marrow Diseases Precancerous Conditions Neoplasms Epoetin Alfa Luspatercept Hematinics |