Clinical trial NCT03682536: 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: 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) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Keywords: Luspatercept
ACE-536
Anemia
Myelodysplastic Syndromes
Blood Transfusion
RBC Transfusion
Erythropoiesis-stimulating agents
Erythropoietin
Myelodysplasia
Epoetin alpha
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
First posted: 2018-09-24
Enrollment: 363
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL
timeFrame: Week 1 through Week 24
Secondary outcomes:
measure: Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 Weeks
timeFrame: Week 1 through Week 24
measure: Mean Hemoglobin Change Over 24 Weeks
timeFrame: Week 1 through Week 24
measure: Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWG
timeFrame: Week 1 through Week 24
measure: Time to Hematologic Improvement - Erythroid Response (HI-E)
timeFrame: Week 1 through Week 24
measure: Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)
timeFrame: Week 1 through Week 24
measure: Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)
timeFrame: Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
measure: Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)
timeFrame: Week 1 through Week 24
measure: Time to First Red Blood Cell (RBC) Transfusion
timeFrame: Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
measure: The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of Treatment
timeFrame: Week 1 through Week 24
measure: Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)
timeFrame: Week 1 through Week 24
measure: Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week Period
timeFrame: Week 1 through Week 48
measure: The Number of Participants With Acute Myeloid Leukemia (AML) Progression
timeFrame: From randomization to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
measure: Median Time to Acute Myeloid Leukemia (AML) Progression
timeFrame: From randomization to first diagnosis of AML up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
measure: Overall Survival (OS)
timeFrame: Randomization to death due to any cause up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)
measure: The Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 42 days post last dose (Up to approximately an average of 72 weeks and a maximum of 208 weeks)
measure: Number of Participants With a Positive Anti-drug Antibody (ADA) Test
timeFrame: Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline and week 24.
measure: Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An)
timeFrame: Baseline, Day 1 on weeks 7,13,19, and 24.
measure: Area Under the Concentration-time Curve [AUC]
timeFrame: Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
measure: Maximum Plasma Concentration of Drug [Cmax]
timeFrame: Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Local Institution - 107
state: California
city: San Diego
country: United States
facility: Local Institution - 115
state: California
city: Whittier
country: United States
facility: Local Institution - 101
state: California
city: New Haven
country: United States
facility: Local Institution - 104
state: Connecticut
city: Washington
country: United States
facility: Local Institution - 136
state: District of Columbia
city: Hudson
country: United States
facility: Local Institution - 119
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 120
state: Florida
city: Tallahassee
country: United States
facility: Local Institution - 122
state: Florida
city: Tampa
country: United States
facility: Local Institution - 108
state: Florida
city: West Palm Beach
country: United States
facility: Local Institution - 118
state: Florida
city: Paducah
country: United States
facility: Local Institution - 102
state: Kentucky
city: Bethesda
country: United States
facility: Local Institution - 123
state: Maryland
city: Kansas City
country: United States
facility: Local Institution - 117
state: Missouri
city: East Brunswick
country: United States
facility: Local Institution - 134
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 113
state: New Jersey
city: Greenville
country: United States
facility: Local Institution - 105
state: North Carolina
city: Portland
country: United States
facility: Local Institution - 131
state: Oregon
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh Medical Center
state: Pennsylvania
city: Rock Hill
country: United States
facility: Local Institution - 111
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Local Institution - 109
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 114
state: Utah
city: Charlottesville
country: United States
facility: Local Institution - 132
state: Virginia
city: Chesapeake
country: United States
facility: Local Institution - 127
state: Virginia
city: Albury
country: Australia
facility: Local Institution - 206
state: New South Wales
city: Blacktown
country: Australia
facility: Local Institution - 213
state: New South Wales
city: Concord
country: Australia
facility: Local Institution - 200
state: New South Wales
city: Kogarah
country: Australia
facility: Local Institution - 215
state: New South Wales
city: Nowra
country: Australia
facility: Local Institution - 211
state: New South Wales
city: Waratah
country: Australia
facility: Local Institution - 210
state: New South Wales
city: Wollongong
country: Australia
facility: Local Institution - 207
state: New South Wales
city: Auchenflower
country: Australia
facility: Local Institution - 208
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 202
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 204
state: Victoria
city: Malvern
country: Australia
facility: Local Institution - 203
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 209
state: Victoria
city: West Perth
country: Australia
facility: Local Institution - 205
state: Western Australia
city: Randwick
country: Australia
facility: Local Institution - 212
city: Linz
country: Austria
facility: Local Institution - 442
city: Vienna
country: Austria
facility: Local Institution - 441
city: Antwerpen
country: Belgium
facility: Local Institution - 475
city: Brasschaat
country: Belgium
facility: Local Institution - 471
city: Brussels
country: Belgium
facility: Local Institution - 474
city: Charleroi
country: Belgium
facility: Local Institution - 472
city: Kortrijk
country: Belgium
facility: Local Institution - 473
city: Leuven
country: Belgium
facility: Local Institution - 470
city: Roeselare
country: Belgium
facility: Local Institution - 476
city: Calgary
country: Canada
facility: Local Institution - 147
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution - 145
state: Alberta
city: Hamilton
country: Canada
facility: Local Institution - 142
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution - 140
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 141
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 144
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 148
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution - 151
state: Saskatchewan
city: Sherbrooke
country: Canada
facility: Local Institution - 152
city: Hradec Kralove
country: Czechia
facility: Local Institution - 560
city: Ostrava-Poruba
country: Czechia
facility: Local Institution - 564
city: Prague 10
country: Czechia
facility: Local Institution - 563
city: Praha 2
country: Czechia
facility: Local Institution - 562
city: Praha
country: Czechia
facility: Local Institution - 561
city: Angers
country: France
facility: Local Institution - 317
city: Bayonne
country: France
facility: Local Institution - 312
city: Caen Cedex 9
country: France
facility: Local Institution - 311
city: La Tronche
country: France
facility: Local Institution - 306
city: Le Mans
country: France
facility: Local Institution - 305
city: Lille
country: France
facility: Local Institution - 309
city: Limoges Cedex
country: France
facility: Local Institution - 303
city: Nantes Cedex 01
country: France
facility: Local Institution - 307
city: Nice Cedex 3
country: France
facility: Local Institution - 301
city: Paris
country: France
facility: Local Institution - 302
city: Paris
country: France
facility: Local Institution - 313
city: Pessac
country: France
facility: Local Institution - 308
city: Pierre Bénite
country: France
facility: Local Institution - 315
city: Poitiers
country: France
facility: Local Institution - 316
city: Strasbourg
country: France
facility: Local Institution - 314
city: Toulouse
country: France
facility: Local Institution - 300
city: Tours cedex
country: France
facility: Local Institution - 310
city: Vandoeuvre les Nancy
country: France
facility: Local Institution - 304
city: Baden-Warttemberg
country: Germany
facility: Local Institution - 422
city: Berlin
country: Germany
facility: Local Institution - 424
city: Dresden
country: Germany
facility: Local Institution - 426
city: Duisburg
country: Germany
facility: Local Institution - 429
city: Dusseldorf
country: Germany
facility: Local Institution - 420
city: Hamburg
country: Germany
facility: Local Institution - 431
city: Keil
country: Germany
facility: Local Institution - 435
city: Koblenz
country: Germany
facility: Local Institution - 423
city: Köln
country: Germany
facility: Local Institution - 428
city: Leipzig
country: Germany
facility: Local Institution - 430
city: Mannheim
country: Germany
facility: Local Institution - 436
city: Munchen
country: Germany
facility: Local Institution - 421
city: Winnenden
country: Germany
facility: Local Institution - 425
city: Würzburg
country: Germany
facility: Local Institution - 427
city: Heraklion
country: Greece
facility: Local Institution - 389
state: Irakleio
city: Alexandroupolis
country: Greece
facility: Local Institution - 396
city: Athens
country: Greece
facility: Local Institution - 397
city: Athens
country: Greece
facility: Local Institution - 391
city: Athens
country: Greece
facility: Local Institution - 392
city: Athina
country: Greece
facility: Local Institution - 395
city: Patras
country: Greece
facility: Local Institution - 398
city: Rio Patras
country: Greece
facility: Local Institution - 393
city: Thessaloniki
country: Greece
facility: Local Institution - 399
city: Thessaloniki
country: Greece
facility: Local Institution - 390
city: Budapest
country: Hungary
facility: Local Institution - 535
city: Debrecen
country: Hungary
facility: Local Institution - 534
city: Nyiregyhaza
country: Hungary
facility: Local Institution - 536
city: Haifa
country: Israel
facility: Local Institution - 386
city: Jerusalem
country: Israel
facility: Local Institution - 383
city: Jerusalem
country: Israel
facility: Local Institution - 384
city: Kfar-Saba
country: Israel
facility: Local Institution - 381
city: Nahariya
country: Israel
facility: Local Institution - 385
city: Tel Aviv
country: Israel
facility: Local Institution - 382
city: Zerifin
country: Israel
facility: Local Institution - 380
city: Orbassano
country: Italy
facility: Local Institution - 331
state: TO
city: Bologna
country: Italy
facility: Local Institution - 324
city: Firenze
country: Italy
facility: Local Institution - 327
city: Meldola
country: Italy
facility: Local Institution - 330
city: Milano
country: Italy
facility: Local Institution - 321
city: Padova
country: Italy
facility: Local Institution - 329
city: Reggio Di Calabria
country: Italy
facility: Local Institution - 326
city: Roma
country: Italy
facility: Local Institution - 328
city: Roma
country: Italy
facility: Local Institution - 332
city: Rome
country: Italy
facility: Local Institution - 325
city: Rozzano
country: Italy
facility: Local Institution - 323
city: Udine
country: Italy
facility: Local Institution - 322
city: Matsuyama
country: Japan
facility: Local Institution - 238
state: Ehime
city: Nagasaki-shi
country: Japan
facility: Local Institution - 244
state: Nagasaki
city: Osakasayama
country: Japan
facility: Local Institution - 236
state: Osaka
city: Amagasaki-Shi
country: Japan
facility: Local Institution - 247
city: Fujisawa-Shi
country: Japan
facility: Local Institution - 249
city: Fukuoka
country: Japan
facility: Local Institution - 234
city: Hitachi, Ibaraki
country: Japan
facility: Local Institution - 237
city: Kamogawa
country: Japan
facility: Local Institution - 231
city: Kitakyushu-Shi
country: Japan
facility: Local Institution - 248
city: Nagaoka-Shi
country: Japan
facility: Local Institution - 270
city: Nagoya-shi
country: Japan
facility: Local Institution - 243
city: Ogaki
country: Japan
facility: Local Institution - 241
city: Okayama
country: Japan
facility: Local Institution - 235
city: Osaka
country: Japan
facility: Local Institution - 242
city: Sagamihara
country: Japan
facility: Local Institution - 233
city: Sapporo-shi
country: Japan
facility: Local Institution - 246
city: Sendai
country: Japan
facility: Local Institution - 239
city: Shibuya-ku
country: Japan
facility: Local Institution - 232
city: Shimotsuga-gun
country: Japan
facility: Local Institution - 245
city: Shinagawa-ku, Tokyo
country: Japan
facility: Local Institution - 230
city: Busan
country: Korea, Republic of
facility: Local Institution - 251
city: Daegu
country: Korea, Republic of
facility: Local Institution - 257
city: Hwasun-Gun
country: Korea, Republic of
facility: Local Institution - 250
city: Seongnamsi
country: Korea, Republic of
facility: Local Institution - 253
city: Seoul
country: Korea, Republic of
facility: Local Institution - 252
city: Seoul
country: Korea, Republic of
facility: Local Institution - 256
city: Seoul
country: Korea, Republic of
facility: Local Institution - 255
city: Seoul
country: Korea, Republic of
facility: Local Institution - 254
city: Kaunas
country: Lithuania
facility: Local Institution - 540
city: Vilnius
country: Lithuania
facility: Local Institution - 541
city: Amsterdam
country: Netherlands
facility: Local Institution - 462
city: Den Haag
country: Netherlands
facility: Local Institution - 461
city: Nijmegen
country: Netherlands
facility: Local Institution - 464
city: Rotterdam
country: Netherlands
facility: Local Institution - 460
city: Sittard-Geleen
country: Netherlands
facility: Local Institution - 463
city: Lodz
country: Poland
facility: Local Institution - 570
state: Lódzkie
city: Gdansk
country: Poland
facility: Local Institution - 575
city: Lubin
country: Poland
facility: Local Institution - 572
city: Poznan
country: Poland
facility: Local Institution - 576
city: Rzwszow
country: Poland
facility: Local Institution - 573
city: Slupsk
country: Poland
facility: Local Institution - 579
city: Walbrzych
country: Poland
facility: Local Institution - 578
city: Wroclaw
country: Poland
facility: Local Institution - 577
city: Wroclaw
country: Poland
facility: Local Institution - 571
city: Beja
country: Portugal
facility: Local Institution - 373
city: Braga
country: Portugal
facility: Local Institution - 371
city: Lisboa
country: Portugal
facility: Local Institution - 372
city: Porto
country: Portugal
facility: Local Institution - 370
city: Setubal
country: Portugal
facility: Local Institution - 374
city: Kaluga
country: Russian Federation
facility: Local Institution - 511
city: Kirov
country: Russian Federation
facility: Local Institution - 505
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution - 509
city: Moscow
country: Russian Federation
facility: Local Institution - 504
city: Moscow
country: Russian Federation
facility: Local Institution - 507
city: Moscow
country: Russian Federation
facility: Local Institution - 500
city: Moscow
country: Russian Federation
facility: Local Institution - 503
city: Saratov
country: Russian Federation
facility: Local Institution - 508
city: St Petersburg
country: Russian Federation
facility: Local Institution - 506
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 510
city: Tula
country: Russian Federation
facility: Local Institution - 502
city: Barcelona
country: Spain
facility: Local Institution - 358
city: Barcelona
country: Spain
facility: Local Institution - 350
city: Granada
country: Spain
facility: Local Institution - 354
city: Madrid
country: Spain
facility: Local Institution - 352
city: Madrid
country: Spain
facility: Local Institution - 355
city: Malaga
country: Spain
facility: Local Institution - 353
city: Murcia
country: Spain
facility: Local Institution - 361
city: Ourense
country: Spain
facility: Local Institution - 356
city: Oviedo
country: Spain
facility: Local Institution - 363
city: Palma de Mallorca
country: Spain
facility: Local Institution - 362
city: Salamanca
country: Spain
facility: Local Institution - 351
city: Seville
country: Spain
facility: Local Institution - 360
city: Valencia
country: Spain
facility: Local Institution - 357
city: Valencia
country: Spain
facility: Local Institution - 359
city: Goteborg
country: Sweden
facility: Local Institution - 550
city: Lund
country: Sweden
facility: Local Institution - 552
city: Stockholm
country: Sweden
facility: Local Institution - 551
city: Bern
country: Switzerland
facility: Local Institution - 450
city: Luzern 16
country: Switzerland
facility: Local Institution - 452
city: Winterthur
country: Switzerland
facility: Local Institution - 451
city: Changhua City, Changhua
country: Taiwan
facility: Local Institution - 220
city: Niaosong District Kaohsiung City
country: Taiwan
facility: Local Institution - 222
city: Taichung City
country: Taiwan
facility: Local Institution - 223
city: Taichung
country: Taiwan
facility: Local Institution - 224
city: Taipei
country: Taiwan
facility: Local Institution - 221
city: Ankara
country: Turkey
facility: Local Institution - 342
city: Manisa
country: Turkey
facility: Local Institution - 340
city: Trabzon
country: Turkey
facility: Local Institution - 343
city: Cherkassy
country: Ukraine
facility: Local Institution - 526
city: Dnipro
country: Ukraine
facility: Local Institution - 525
city: Kyiv
country: Ukraine
facility: Local Institution - 522
city: Lvov
country: Ukraine
facility: Local Institution - 520
city: Mykolaiv
country: Ukraine
facility: Local Institution - 523
city: Ternopil
country: Ukraine
facility: Local Institution - 521
city: Aberdeen
country: United Kingdom
facility: Local Institution - 401
city: Bournemouth
country: United Kingdom
facility: Local Institution - 403
city: Headington, Oxford
country: United Kingdom
facility: Local Institution - 405
city: Lincoln
country: United Kingdom
facility: Local Institution - 407
city: London
country: United Kingdom
facility: Local Institution - 404
city: Manchester
country: United Kingdom
facility: Local Institution - 400
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: