Myelodysplastic Syndromes Clinical Trial
— COMMANDSOfficial 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
| Verified date | November 2023 |
| Source | Celgene |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Active, not recruiting |
| Enrollment | 363 |
| Est. completion date | September 28, 2027 |
| Est. primary completion date | March 31, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Local Institution - 202 | Adelaide | South Australia |
| Australia | Local Institution - 206 | Albury | New South Wales |
| Australia | Local Institution - 208 | Auchenflower | Queensland |
| Australia | Local Institution - 213 | Blacktown | New South Wales |
| Australia | Local Institution - 204 | Clayton | Victoria |
| Australia | Local Institution - 200 | Concord | New South Wales |
| Australia | Local Institution - 215 | Kogarah | New South Wales |
| Australia | Local Institution - 203 | Malvern | Victoria |
| Australia | Local Institution - 209 | Melbourne | Victoria |
| Australia | Local Institution - 211 | Nowra | New South Wales |
| Australia | Local Institution - 212 | Randwick | |
| Australia | Local Institution - 210 | Waratah | New South Wales |
| Australia | Local Institution - 205 | West Perth | Western Australia |
| Australia | Local Institution - 207 | Wollongong | New South Wales |
| Austria | Local Institution - 442 | Linz | |
| Austria | Local Institution - 441 | Vienna | |
| Belgium | Local Institution - 475 | Antwerpen | |
| Belgium | Local Institution - 471 | Brasschaat | |
| Belgium | Local Institution - 474 | Brussels | |
| Belgium | Local Institution - 472 | Charleroi | |
| Belgium | Local Institution - 473 | Kortrijk | |
| Belgium | Local Institution - 470 | Leuven | |
| Belgium | Local Institution - 476 | Roeselare | |
| Canada | Local Institution - 147 | Calgary | Alberta |
| Canada | Local Institution - 145 | Edmonton | Alberta |
| Canada | Local Institution - 142 | Hamilton | Ontario |
| Canada | Local Institution - 144 | Montreal | Quebec |
| Canada | Local Institution - 148 | Montreal | Quebec |
| Canada | Local Institution - 140 | Ottawa | Ontario |
| Canada | Local Institution - 151 | Saskatoon | Saskatchewan |
| Canada | Local Institution - 152 | Sherbrooke | |
| Canada | Local Institution - 141 | Toronto | Ontario |
| Czechia | Local Institution - 560 | Hradec Kralove | |
| Czechia | Local Institution - 564 | Ostrava-Poruba | |
| Czechia | Local Institution - 563 | Prague 10 | |
| Czechia | Local Institution - 561 | Praha | |
| Czechia | Local Institution - 562 | Praha 2 | |
| France | Local Institution - 317 | Angers | |
| France | Local Institution - 312 | Bayonne | |
| France | Local Institution - 311 | Caen Cedex 9 | |
| France | Local Institution - 306 | La Tronche | |
| France | Local Institution - 305 | Le Mans | |
| France | Local Institution - 309 | Lille | |
| France | Local Institution - 303 | Limoges Cedex | |
| France | Local Institution - 307 | Nantes Cedex 01 | |
| France | Local Institution - 301 | Nice Cedex 3 | |
| France | Local Institution - 302 | Paris | |
| France | Local Institution - 313 | Paris | |
| France | Local Institution - 308 | Pessac | |
| France | Local Institution - 315 | Pierre Bénite | |
| France | Local Institution - 316 | Poitiers | |
| France | Local Institution - 314 | Strasbourg | |
| France | Local Institution - 300 | Toulouse | |
| France | Local Institution - 310 | Tours cedex | |
| France | Local Institution - 304 | Vandoeuvre les Nancy | |
| Germany | Local Institution - 422 | Baden-Warttemberg | |
| Germany | Local Institution - 424 | Berlin | |
| Germany | Local Institution - 426 | Dresden | |
| Germany | Local Institution - 429 | Duisburg | |
| Germany | Local Institution - 420 | Dusseldorf | |
| Germany | Local Institution - 431 | Hamburg | |
| Germany | Local Institution - 435 | Keil | |
| Germany | Local Institution - 423 | Koblenz | |
| Germany | Local Institution - 428 | Köln | |
| Germany | Local Institution - 430 | Leipzig | |
| Germany | Local Institution - 436 | Mannheim | |
| Germany | Local Institution - 421 | Munchen | |
| Germany | Local Institution - 425 | Winnenden | |
| Germany | Local Institution - 427 | Würzburg | |
| Greece | Local Institution - 396 | Alexandroupolis | |
| Greece | Local Institution - 391 | Athens | |
| Greece | Local Institution - 392 | Athens | |
| Greece | Local Institution - 397 | Athens | |
| Greece | Local Institution - 395 | Athina | |
| Greece | Local Institution - 389 | Heraklion | Irakleio |
| Greece | Local Institution - 398 | Patras | |
| Greece | Local Institution - 393 | Rio Patras | |
| Greece | Local Institution - 390 | Thessaloniki | |
| Greece | Local Institution - 399 | Thessaloniki | |
| Hungary | Local Institution - 535 | Budapest | |
| Hungary | Local Institution - 534 | Debrecen | |
| Hungary | Local Institution - 536 | Nyiregyhaza | |
| Israel | Local Institution - 386 | Haifa | |
| Israel | Local Institution - 383 | Jerusalem | |
| Israel | Local Institution - 384 | Jerusalem | |
| Israel | Local Institution - 381 | Kfar-Saba | |
| Israel | Local Institution - 385 | Nahariya | |
| Israel | Local Institution - 382 | Tel Aviv | |
| Israel | Local Institution - 380 | Zerifin | |
| Italy | Local Institution - 324 | Bologna | |
| Italy | Local Institution - 327 | Firenze | |
| Italy | Local Institution - 330 | Meldola | |
| Italy | Local Institution - 321 | Milano | |
| Italy | Local Institution - 331 | Orbassano | TO |
| Italy | Local Institution - 329 | Padova | |
| Italy | Local Institution - 326 | Reggio Di Calabria | |
| Italy | Local Institution - 328 | Roma | |
| Italy | Local Institution - 332 | Roma | |
| Italy | Local Institution - 325 | Rome | |
| Italy | Local Institution - 323 | Rozzano | |
| Italy | Local Institution - 322 | Udine | |
| Japan | Local Institution - 247 | Amagasaki-Shi | |
| Japan | Local Institution - 249 | Fujisawa-Shi | |
| Japan | Local Institution - 234 | Fukuoka | |
| Japan | Local Institution - 237 | Hitachi, Ibaraki | |
| Japan | Local Institution - 231 | Kamogawa | |
| Japan | Local Institution - 248 | Kitakyushu-Shi | |
| Japan | Local Institution - 238 | Matsuyama | Ehime |
| Japan | Local Institution - 270 | Nagaoka-Shi | |
| Japan | Local Institution - 244 | Nagasaki-shi | Nagasaki |
| Japan | Local Institution - 243 | Nagoya-shi | |
| Japan | Local Institution - 241 | Ogaki | |
| Japan | Local Institution - 235 | Okayama | |
| Japan | Local Institution - 242 | Osaka | |
| Japan | Local Institution - 236 | Osakasayama | Osaka |
| Japan | Local Institution - 233 | Sagamihara | |
| Japan | Local Institution - 246 | Sapporo-shi | |
| Japan | Local Institution - 239 | Sendai | |
| Japan | Local Institution - 232 | Shibuya-ku | |
| Japan | Local Institution - 245 | Shimotsuga-gun | |
| Japan | Local Institution - 230 | Shinagawa-ku, Tokyo | |
| Korea, Republic of | Local Institution - 251 | Busan | |
| Korea, Republic of | Local Institution - 257 | Daegu | |
| Korea, Republic of | Local Institution - 250 | Hwasun-Gun | |
| Korea, Republic of | Local Institution - 253 | Seongnam-si | |
| Korea, Republic of | Local Institution - 252 | Seoul | |
| Korea, Republic of | Local Institution - 254 | Seoul | |
| Korea, Republic of | Local Institution - 255 | Seoul | |
| Korea, Republic of | Local Institution - 256 | Seoul | |
| Lithuania | Local Institution - 540 | Kaunas | |
| Lithuania | Local Institution - 541 | Vilnius | |
| Netherlands | Local Institution - 462 | Amsterdam | |
| Netherlands | Local Institution - 461 | Den Haag | |
| Netherlands | Local Institution - 464 | Nijmegen | |
| Netherlands | Local Institution - 460 | Rotterdam | |
| Netherlands | Local Institution - 463 | Sittard-Geleen | |
| Poland | Local Institution - 575 | Gdansk | |
| Poland | Local Institution - 570 | Lodz | Lódzkie |
| Poland | Local Institution - 572 | Lubin | |
| Poland | Local Institution - 576 | Poznan | |
| Poland | Local Institution - 573 | Rzwszow | |
| Poland | Local Institution - 579 | Slupsk | |
| Poland | Local Institution - 578 | Walbrzych | |
| Poland | Local Institution - 571 | Wroclaw | |
| Poland | Local Institution - 577 | Wroclaw | |
| Portugal | Local Institution - 373 | Beja | |
| Portugal | Local Institution - 371 | Braga | |
| Portugal | Local Institution - 372 | Lisboa | |
| Portugal | Local Institution - 370 | Porto | |
| Portugal | Local Institution - 374 | Setubal | |
| Russian Federation | Local Institution - 511 | Kaluga | |
| Russian Federation | Local Institution - 505 | Kirov | |
| Russian Federation | Local Institution - 509 | Krasnoyarsk | |
| Russian Federation | Local Institution - 500 | Moscow | |
| Russian Federation | Local Institution - 503 | Moscow | |
| Russian Federation | Local Institution - 504 | Moscow | |
| Russian Federation | Local Institution - 507 | Moscow | |
| Russian Federation | Local Institution - 508 | Saratov | |
| Russian Federation | Local Institution - 506 | St Petersburg | |
| Russian Federation | Local Institution - 510 | St. Petersburg | |
| Russian Federation | Local Institution - 502 | Tula | |
| Spain | Local Institution - 350 | Barcelona | |
| Spain | Local Institution - 358 | Barcelona | |
| Spain | Local Institution - 354 | Granada | |
| Spain | Local Institution - 352 | Madrid | |
| Spain | Local Institution - 355 | Madrid | |
| Spain | Local Institution - 353 | Malaga | |
| Spain | Local Institution - 361 | Murcia | |
| Spain | Local Institution - 356 | Ourense | |
| Spain | Local Institution - 363 | Oviedo | |
| Spain | Local Institution - 362 | Palma de Mallorca | |
| Spain | Local Institution - 351 | Salamanca | |
| Spain | Local Institution - 360 | Seville | |
| Spain | Local Institution - 357 | Valencia | |
| Spain | Local Institution - 359 | Valencia | |
| Sweden | Local Institution - 550 | Goteborg | |
| Sweden | Local Institution - 552 | Lund | |
| Sweden | Local Institution - 551 | Stockholm | |
| Switzerland | Local Institution - 450 | Bern | |
| Switzerland | Local Institution - 452 | Luzern 16 | |
| Switzerland | Local Institution - 451 | Winterthur | |
| Taiwan | Local Institution - 220 | Changhua City, Changhua | |
| Taiwan | Local Institution - 222 | Niaosong District Kaohsiung City | |
| Taiwan | Local Institution - 224 | Taichung | |
| Taiwan | Local Institution - 223 | Taichung City | |
| Taiwan | Local Institution - 221 | Taipei, Zhongzheng Dist. | |
| Turkey | Local Institution - 342 | Ankara | |
| Turkey | Local Institution - 340 | Manisa | |
| Turkey | Local Institution - 343 | Trabzon | |
| Ukraine | Local Institution - 526 | Cherkassy | |
| Ukraine | Local Institution - 525 | Dnipro | |
| Ukraine | Local Institution - 522 | Kyiv | |
| Ukraine | Local Institution - 520 | Lvov | |
| Ukraine | Local Institution - 523 | Mykolaiv | |
| Ukraine | Local Institution - 521 | Ternopil | |
| United Kingdom | Local Institution - 401 | Aberdeen | |
| United Kingdom | Local Institution - 403 | Bournemouth | |
| United Kingdom | Local Institution - 405 | Headington, Oxford | |
| United Kingdom | Local Institution - 407 | Lincoln | |
| United Kingdom | Local Institution - 404 | London | |
| United Kingdom | Local Institution - 400 | Manchester | |
| United States | Local Institution - 107 | Berkeley | California |
| United States | Local Institution - 123 | Bethesda | Maryland |
| United States | Local Institution - 132 | Charlottesville | Virginia |
| United States | Local Institution - 127 | Chesapeake | Virginia |
| United States | Baylor University Medical Center | Dallas | Texas |
| United States | Local Institution - 134 | East Brunswick | New Jersey |
| United States | Local Institution - 105 | Greenville | North Carolina |
| United States | Local Institution - 113 | Hackensack | New Jersey |
| United States | Local Institution - 109 | Houston | Texas |
| United States | Local Institution - 119 | Hudson | Florida |
| United States | Local Institution - 117 | Kansas City | Missouri |
| United States | Tennessee Oncology | Nashville | Tennessee |
| United States | Local Institution - 104 | New Haven | Connecticut |
| United States | Local Institution - 102 | Paducah | Kentucky |
| United States | Univ of Pittsburgh Medical Center | Pittsburgh | Pennsylvania |
| United States | Local Institution - 131 | Portland | Oregon |
| United States | Local Institution - 111 | Rock Hill | South Carolina |
| United States | Local Institution - 120 | Saint Petersburg | Florida |
| United States | Utah Cancer Specialists - South Salt Lake | Salt Lake City | Utah |
| United States | Local Institution - 115 | San Diego | California |
| United States | Local Institution - 122 | Tallahassee | Florida |
| United States | Local Institution - 108 | Tampa | Florida |
| United States | Local Institution - 136 | Washington | District of Columbia |
| United States | Local Institution - 118 | West Palm Beach | Florida |
| United States | Local Institution - 101 | Whittier | California |
| Lead Sponsor | Collaborator |
|---|---|
| Celgene | Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA |
United States, 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,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | RBC-TI for 24 weeks | Week 1 through Week 24 | ||
| Secondary | Mean hemoglobin change over 24 weeks | Week 1 through Week 24 | ||
| Secondary | Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG) | Week 1 through Week 24 | ||
| Secondary | Time to HI-E | Week 1 through Week 24 | ||
| Secondary | RBC-TI for = 12 weeks (84 days) | Week 1 through Week 24 | ||
| Secondary | Duration of RBC-TI = 12 weeks (84 days) | Week 1 through End of Treatment (EOT), up to approximately 60 months | ||
| Secondary | Time to RBC-TI = 12 weeks (84 days) | Week 1 through Week 24 | ||
| Secondary | Time to first red blood cell (RBC) transfusion | Week 1 through EOT, up to approximately 60 months | ||
| Secondary | RBC transfusion burden on treatment | Week 1 through Week 24 | ||
| Secondary | RBC-TI for = 56 days (8 weeks) | Week 1 through Week 24 | ||
| Secondary | RBC-TI for a consecutive 24-week period | Week 1 through Week 48 | ||
| Secondary | The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) | Screening through Week 24 | ||
| Secondary | The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire | Screening through Week 24 | ||
| Secondary | Number of participants with Adverse Events (AEs) | Week 1 through 42 days post last dose | ||
| Secondary | Pharmacokinetic - area under the concentration-time curve (AUC) | Randomization through 1-year post first dose | ||
| Secondary | Pharmacokinetic - maximum plasma concentration of drug (Cmax) | Randomization through 1-year post first dose | ||
| Secondary | Frequency of antidrug antibodies (ADA) | Randomization through 1-year post first dose | ||
| Secondary | Number of participants progressing to acute myeloid leukemia (AML) | Randomization through up to 60 months | ||
| Secondary | Percentage of participants progressing to AML | Randomization through up to 60 months | ||
| Secondary | Time to AML progression | Randomization through up to 60 months | ||
| Secondary | Overall survival | Randomization through up to 60 months |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
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