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)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Luspatercept; Drug: Epoetin alfa

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Randwick, Australia, 2031
    • Local Institution - 212
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Local Institution - 206
    • Blacktown, New South Wales, Australia, 2148
      • Local Institution - 213
    • Concord, New South Wales, Australia, 2139
      • Local Institution - 200
    • Kogarah, New South Wales, Australia, 2217
      • Local Institution - 215
    • Nowra, New South Wales, Australia, 2541
      • Local Institution - 211
    • Waratah, New South Wales, Australia, 2298
      • Local Institution - 210
    • Wollongong, New South Wales, Australia, 2500
      • Local Institution - 207
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Local Institution - 208
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 202
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 204
    • Malvern, Victoria, Australia, 3144
      • Local Institution - 203
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 209
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Local Institution - 205
• Austria
  • Linz, Austria, 4020
    • Local Institution - 442
  • Vienna, Austria, 1090
    • Local Institution - 441
• Belgium
  • Antwerpen, Belgium, 2020
    • Local Institution - 475
  • Brasschaat, Belgium, 2930
    • Local Institution - 471
  • Brussels, Belgium, 1200
    • Local Institution - 474
  • Charleroi, Belgium, 6000
    • Local Institution - 472
  • Kortrijk, Belgium, 8500
    • Local Institution - 473
  • Leuven, Belgium, 3000
    • Local Institution - 470
  • Roeselare, Belgium, 8800
    • Local Institution - 476
• Canada
  • Sherbrooke, Canada, J1H 5N4
    • Local Institution - 152
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 147
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution - 145
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 142
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 140
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 141
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Local Institution - 144
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 148
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Local Institution - 151
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Local Institution - 560
  • Ostrava-Poruba, Czechia, 708 52
    • Local Institution - 564
  • Prague 10, Czechia, 100 34
    • Local Institution - 563
  • Praha, Czechia, 128 20
    • Local Institution - 561
  • Praha 2, Czechia, 128 08
    • Local Institution - 562
• France
  • Angers, France, 49000
    • Local Institution - 317
  • Bayonne, France, 64109
    • Local Institution - 312
  • Caen Cedex 9, France, 14033
    • Local Institution - 311
  • La Tronche, France, 38700
    • Local Institution - 306
  • Le Mans, France, 72037
    • Local Institution - 305
  • Lille, France, 59037
    • Local Institution - 309
  • Limoges Cedex, France, 87042
    • Local Institution - 303
  • Nantes Cedex 01, France, 44093
    • Local Institution - 307
  • Nice Cedex 3, France, 06200
    • Local Institution - 301
  • Paris, France, 75010
    • Local Institution - 302
  • Paris, France, 75014
    • Local Institution - 313
  • Pessac, France, 33604
    • Local Institution - 308
  • Pierre Bénite, France, 69495
    • Local Institution - 315
  • Poitiers, France, 86021
    • Local Institution - 316
  • Strasbourg, France, 67033
    • Local Institution - 314
  • Toulouse, France, 31059
    • Local Institution - 300
  • Tours cedex, France, 37044
    • Local Institution - 310
  • Vandoeuvre les Nancy, France, 54511
    • Local Institution - 304
• Germany
  • Baden-Warttemberg, Germany, 73557
    • Local Institution - 422
  • Berlin, Germany, 14195
    • Local Institution - 424
  • Dresden, Germany, 01307
    • Local Institution - 426
  • Duisburg, Germany, 47166
    • Local Institution - 429
  • Dusseldorf, Germany, 40479
    • Local Institution - 420
  • Hamburg, Germany, 22081
    • Local Institution - 431
  • Keil, Germany, 24105
    • Local Institution - 435
  • Koblenz, Germany, 56068
    • Local Institution - 423
  • Köln, Germany, 50677
    • Local Institution - 428
  • Leipzig, Germany, 04103
    • Local Institution - 430
  • Mannheim, Germany, 68167
    • Local Institution - 436
  • Munchen, Germany, 81675
    • Local Institution - 421
  • Winnenden, Germany, 71364
    • Local Institution - 425
  • Würzburg, Germany, 97070
    • Local Institution - 427
• Greece
  • Alexandroupolis, Greece, 08100
    • Local Institution - 396
  • Athens, Greece, 10676
    • Local Institution - 397
  • Athens, Greece, 115 27
    • Local Institution - 391
  • Athens, Greece, 12464
    • Local Institution - 392
  • Athina, Greece, 115 27
    • Local Institution - 395
  • Patras, Greece, 26500
    • Local Institution - 398
  • Rio Patras, Greece, 26500
    • Local Institution - 393
  • Thessaloniki, Greece, 546 36
    • Local Institution - 399
  • Thessaloniki, Greece, 57010
    • Local Institution - 390
  • Irakleio
    • Heraklion, Irakleio, Greece, 71110
      • Local Institution - 389
• Hungary
  • Budapest, Hungary, 1096
    • Local Institution - 535
  • Debrecen, Hungary, 4032
    • Local Institution - 534
  • Nyiregyhaza, Hungary, 4400
    • Local Institution - 536
• Israel
  • Haifa, Israel, 34362
    • Local Institution - 386
  • Jerusalem, Israel, 91031
    • Local Institution - 383
  • Jerusalem, Israel, 91120
    • Local Institution - 384
  • Kfar-Saba, Israel, 44281
    • Local Institution - 381
  • Nahariya, Israel, 22100
    • Local Institution - 385
  • Tel Aviv, Israel, 64239
    • Local Institution - 382
  • Zerifin, Israel, 70300
    • Local Institution - 380
• Italy
  • Bologna, Italy, 40138
    • Local Institution - 324
  • Firenze, Italy, 50134
    • Local Institution - 327
  • Meldola, Italy, 47014
    • Local Institution - 330
  • Milano, Italy, 20162
    • Local Institution - 321
  • Padova, Italy, 35128
    • Local Institution - 329
  • Reggio Di Calabria, Italy, 89124
    • Local Institution - 326
  • Roma, Italy, 00133
    • Local Institution - 328
  • Roma, Italy, 00189
    • Local Institution - 332
  • Rome, Italy, 00161
    • Local Institution - 325
  • Rozzano, Italy, 20089
    • Local Institution - 323
  • Udine, Italy, 33100
    • Local Institution - 322
  • TO
    • Orbassano, TO, Italy, 10043
      • Local Institution - 331
• Japan
  • Amagasaki-Shi, Japan, 660-0892
    • Local Institution - 247
  • Fujisawa-Shi, Japan, 251-0052
    • Local Institution - 249
  • Fukuoka, Japan, 810-8563
    • Local Institution - 234
  • Hitachi, Ibaraki, Japan, 317-0077
    • Local Institution - 237
  • Kamogawa, Japan, 296-8602
    • Local Institution - 231
  • Kitakyushu-Shi, Japan, 806-0034
    • Local Institution - 248
  • Nagaoka-Shi, Japan, 940-2108
    • Local Institution - 270
  • Nagoya-shi, Japan, 460-0001
    • Local Institution - 243
  • Ogaki, Japan, 503-8502
    • Local Institution - 241
  • Okayama, Japan, 700-8557
    • Local Institution - 235
  • Osaka, Japan, 545-8586
    • Local Institution - 242
  • Sagamihara, Japan, 252-0375
    • Local Institution - 233
  • Sapporo-shi, Japan, 064-0804
    • Local Institution - 246
  • Sendai, Japan, 980-8574
    • Local Institution - 239
  • Shibuya-ku, Japan, 150-8935
    • Local Institution - 232
  • Shimotsuga-gun, Japan, 321-0293
    • Local Institution - 245
  • Shinagawa-ku, Tokyo, Japan, 141-8625
    • Local Institution - 230
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Local Institution - 238
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8511
      • Local Institution - 244
  • Osaka
    • Osakasayama, Osaka, Japan, 5898511
      • Local Institution - 236
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Local Institution - 251
  • Daegu, Korea, Republic of, 700-721
    • Local Institution - 257
  • Hwasun-Gun, Korea, Republic of, 58128
    • Local Institution - 250
  • Seongnam-si, Korea, Republic of, 13620
    • Local Institution - 253
  • Seoul, Korea, Republic of, 06591
    • Local Institution - 256
  • Seoul, Korea, Republic of, 3080
    • Local Institution - 255
  • Seoul, Korea, Republic of, 5505
    • Local Institution - 254
  • Seoul, Korea, Republic of, 06351
    • Local Institution - 252
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Local Institution - 540
  • Vilnius, Lithuania, LT-08661
    • Local Institution - 541
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 462
  • Den Haag, Netherlands, 2545 CH
    • Local Institution - 461
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 464
  • Rotterdam, Netherlands, 3015 CE
    • Local Institution - 460
  • Sittard-Geleen, Netherlands, 6162 BG
    • Local Institution - 463
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution - 575
  • Lubin, Poland, 20-081
    • Local Institution - 572
  • Poznan, Poland, 60-569
    • Local Institution - 576
  • Rzwszow, Poland, 35-055
    • Local Institution - 573
  • Slupsk, Poland, 76-200
    • Local Institution - 579
  • Walbrzych, Poland, 58-309
    • Local Institution - 578
  • Wroclaw, Poland, 50-367
    • Local Institution - 577
  • Wroclaw, Poland, 50-556
    • Local Institution - 571
  • Lódzkie
    • Lodz, Lódzkie, Poland, 93-513
      • Local Institution - 570
• Portugal
  • Beja, Portugal, 7801-849
    • Local Institution - 373
  • Braga, Portugal, 4710-243
    • Local Institution - 371
  • Lisboa, Portugal, 1099-023
    • Local Institution - 372
  • Porto, Portugal, 4200-072
    • Local Institution - 370
  • Setubal, Portugal, 2910-446
    • Local Institution - 374
• Russian Federation
  • Kaluga, Russian Federation, 248007
    • Local Institution - 511
  • Kirov, Russian Federation, 610027
    • Local Institution - 505
  • Krasnoyarsk, Russian Federation, 660022
    • Local Institution - 509
  • Moscow, Russian Federation, 111123
    • Local Institution - 504
  • Moscow, Russian Federation, 125284
    • Local Institution - 500
  • Moscow, Russian Federation, 123182
    • Local Institution - 507
  • Moscow, Russian Federation, 129301
    • Local Institution - 503
  • Saratov, Russian Federation, 410012
    • Local Institution - 508
  • St Petersburg, Russian Federation, 197341
    • Local Institution - 506
  • St. Petersburg, Russian Federation, 197022
    • Local Institution - 510
  • Tula, Russian Federation, 300053
    • Local Institution - 502
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 358
  • Barcelona, Spain, 08908
    • Local Institution - 350
  • Granada, Spain, 18014
    • Local Institution - 354
  • Madrid, Spain, 28007
    • Local Institution - 352
  • Madrid, Spain, 28041
    • Local Institution - 355
  • Malaga, Spain, 29010
    • Local Institution - 353
  • Murcia, Spain, 30008
    • Local Institution - 361
  • Ourense, Spain, 32005
    • Local Institution - 356
  • Oviedo, Spain, 33011
    • Local Institution - 363
  • Palma de Mallorca, Spain, 7120
    • Local Institution - 362
  • Salamanca, Spain, 37007
    • Local Institution - 351
  • Seville, Spain, 41013
    • Local Institution - 360
  • Valencia, Spain, 46010
    • Local Institution - 357
  • Valencia, Spain, 46026
    • Local Institution - 359
• Sweden
  • Goteborg, Sweden, SE-413 45
    • Local Institution - 550
  • Lund, Sweden, SE-221 85
    • Local Institution - 552
  • Stockholm, Sweden, SE-141 86
    • Local Institution - 551
• Switzerland
  • Bern, Switzerland, 3010
    • Local Institution - 450
  • Luzern 16, Switzerland, 6000
    • Local Institution - 452
  • Winterthur, Switzerland, 8400
    • Local Institution - 451
• Taiwan
  • Changhua City, Changhua, Taiwan, 500
    • Local Institution - 220
  • Niaosong District Kaohsiung City, Taiwan, 83301
    • Local Institution - 222
  • Taichung, Taiwan, 40705
    • Local Institution - 224
  • Taichung City, Taiwan, 40447
    • Local Institution - 223
  • Taipei, Zhongzheng Dist., Taiwan, 10002
    • Local Institution - 221
• Turkey
  • Ankara, Turkey, 06100
    • Local Institution - 342
  • Manisa, Turkey, 45030
    • Local Institution - 340
  • Trabzon, Turkey, 61080
    • Local Institution - 343
• Ukraine
  • Cherkassy, Ukraine, 18009
    • Local Institution - 526
  • Dnipro, Ukraine, 49102
    • Local Institution - 525
  • Kyiv, Ukraine, 3115
    • Local Institution - 522
  • Lvov, Ukraine, 79044
    • Local Institution - 520
  • Mykolaiv, Ukraine, 54058
    • Local Institution - 523
  • Ternopil, Ukraine, 46002
    • Local Institution - 521
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Local Institution - 401
  • Bournemouth, United Kingdom, BH7 7DW
    • Local Institution - 403
  • Headington, Oxford, United Kingdom, OX3 7LE
    • Local Institution - 405
  • Lincoln, United Kingdom, LN2 5QY
    • Local Institution - 407
  • London, United Kingdom, SE5 9RS
    • Local Institution - 404
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 400
• United States
  • California
    • Berkeley, California, United States, 94704
      • Local Institution - 107
    • San Diego, California, United States, 92123
      • Local Institution - 115
    • Whittier, California, United States, 90603
      • Local Institution - 101
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 104
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Local Institution - 136
  • Florida
    • Hudson, Florida, United States, 34667
      • Local Institution - 119
    • Saint Petersburg, Florida, United States, 33705
      • Local Institution - 120
    • Tallahassee, Florida, United States, 32308
      • Local Institution - 122
    • Tampa, Florida, United States, 33612
      • Local Institution - 108
    • West Palm Beach, Florida, United States, 33401
      • Local Institution - 118
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Local Institution - 102
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Local Institution - 123
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Local Institution - 117
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Local Institution - 134
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 113
  • North Carolina
    • Greenville, North Carolina, United States, 27858-4354
      • Local Institution - 105
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 131
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Univ of Pittsburgh Medical Center
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Local Institution - 111
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1625
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Local Institution - 109
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists - South Salt Lake
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Local Institution - 132
    • Chesapeake, Virginia, United States, 23320
      • Local Institution - 127

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Luspatercept	Drug: Luspatercept; Specified dose on specified days; Other Names: ACE-536
Active Comparator: Epoetin alfa	Drug: Epoetin alfa; Specified dose on specified days; Other Names: EPREX®; ERYPO®; PROCRIT®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Red blood cell transfusion independence (RBC-TI) for 12 weeks (84 days) with a mean hemoglobin increase ≥ 1.5 g/dL	Week 1 through Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
RBC-TI for 24 weeks	Week 1 through Week 24
Mean hemoglobin change over 24 weeks	Week 1 through Week 24
Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG)	Week 1 through Week 24
Time to HI-E	Week 1 through Week 24
RBC-TI for ≥ 12 weeks (84 days)	Week 1 through Week 24
Duration of RBC-TI ≥ 12 weeks (84 days)	Week 1 through End of Treatment (EOT), up to approximately 60 months
Time to RBC-TI ≥ 12 weeks (84 days)	Week 1 through Week 24
Time to first red blood cell (RBC) transfusion	Week 1 through EOT, up to approximately 60 months
RBC transfusion burden on treatment	Week 1 through Week 24
RBC-TI for ≥ 56 days (8 weeks)	Week 1 through Week 24
RBC-TI for a consecutive 24-week period	Week 1 through Week 48
The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30)	Screening through Week 24
The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire	Screening through Week 24
Number of participants with Adverse Events (AEs)	Week 1 through 42 days post last dose
Pharmacokinetic - area under the concentration-time curve (AUC)	Randomization through 1-year post first dose
Pharmacokinetic - maximum plasma concentration of drug (Cmax)	Randomization through 1-year post first dose
Frequency of antidrug antibodies (ADA)	Randomization through 1-year post first dose
Number of participants progressing to acute myeloid leukemia (AML)	Randomization through up to 60 months
Percentage of participants progressing to AML	Randomization through up to 60 months
Time to AML progression	Randomization through up to 60 months
Overall survival	Randomization through up to 60 months

Collaborators and Investigators

• Sponsor: Celgene
• Collaborators: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): September 28, 2027

Study Registration Dates

• First Submitted: September 7, 2018
• First Submitted That Met QC Criteria: September 20, 2018
• First Posted (Actual): September 24, 2018

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Erythropoietin; Anemia; Blood Transfusion; Myelodysplastic Syndromes; Luspatercept; ACE-536; Myelodysplasia; RBC Transfusion; Erythropoiesis-stimulating agents
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Anemia; Hematinics; Epoetin Alfa; Luspatercept
• Other Study ID Numbers: ACE-536-MDS-002; U1111-1218-1810 (Registry Identifier: WHO); 2022-501485-22-00 (Other Identifier: EU CTR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No