A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

NCT02631070 | Completed Phase 3 Results DMC

• 2 other identifiers: ACE-536-MDS-0012015-003454-41
• Study Type: interventional
• Target: 229
• Locations: 11 countries
• Sites: 74

Brief Summary

The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in participants with anemia due to the Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate MDS with ring sideroblasts who require red blood cell (RBC) transfusions.

Conditions

Myelodysplastic Syndromes

Keywords

Luspatercept; Transfusion dependent; Lower risk; Low risk; Myelodysplastic Syndromes; ESA refractory; ESA intolerant; ESA ineligible; ACE-536; Anemia; Ring Sideroblasts; Require Red Blood Cell Transfusions; MEDALIST; MDS; IPSS-R very low/IPSS-R low/IPSS-R intermediate

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24

  RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders.

  From Week 1 through Week 24 of study treatment

Secondary Outcomes (27)

• Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24

  From Week 1 through Week 24 of study treatment

• Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48

  From Week 1 through Week 48 of study treatment

• Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48

  From Week 1 through Week 48 of study treatment

• Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period

  At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48

• Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period

  Week 1 through 24 or Week 1 Through Week 48

Study Arms (2)

Experimental Arm - Luspatercept (ACE-536)

EXPERIMENTAL

Starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks

Drug: Luspatercept

Control Arm: Placebo

PLACEBO COMPARATOR

Subcutaneous injection every 3 weeks

Other: Placebo

Interventions

Luspatercept DRUG

Also known as: ACE-536

Experimental Arm - Luspatercept (ACE-536)

Placebo OTHER

Control Arm: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
• Documented diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets IPSS R classification of very low, low, or intermediate risk disease, and:
• Ring sideroblast ≥ 15% of erythroid precursors in bone marrow or ≥ 5% (but \< 15%) if SF3B1 mutation is present.
• \< 5% blasts in bone marrow
• Peripheral blood white blood cell (WBC) count \< 13,000/µL 3. Requires red blood cell RBC transfusions 4. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 5. Subjects who are refractory/intolerant/ineligible to prior erythropoietin-stimulating agents (ESA) treatment, defined as:
• Refractory to prior - erythropoietin stimulating agents treatment: documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with granulocyte colony stimulating factor (G-CSF); ESA regimen must have been either recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent OR darbepoetin alpha ≥ 500 μg Q3W for at least 4 doses or equivalent
• Intolerant to prior ESA treatment: documentation of discontinuation of prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event
• ESA ineligible: low chance of response to ESA base on endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Prior therapy with disease modifying agents for underlying MDS disease.
• Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• MDS associated with del 5q cytogenetic abnormality
• Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• \- iron deficiency to be determined by serum ferritin less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity less than or equal to 20%\] or bone marrow aspirate stain for iron).
• Prior allogeneic or autologous stem cell transplant
• Known history of diagnosis of acute myeloid leukemia (AML)
• Use of any of the following within 5 weeks prior to randomization:
• anticancer cytotoxic chemotherapeutic agent or treatment
• corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS
• iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization
• other RBC hematopoietic growth factors (eg, Interleukin-3)
• investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to randomization or within 5 weeks, whichever is longer is excluded.

Sponsors & Collaborators

• Celgene: lead
• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: collaborator

Study Sites (74)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Ochsner Medical Institutions

New Orleans, Louisiana, 70123, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Columbia-Presbyterian Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center Albert Einstein Cancer Center

The Bronx, New York, 10467, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, 44195-0001, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Algemeen Ziekenhuis Klina

Brasschaat, 2930, Belgium

Location

AZ Sint-Jan AV Brugge

Bruges, 8000, Belgium

Location

UZ Brussels

Brussels, 1090, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Cliniques Universitaires UCL de Mont-Godine

Yvoir, 5530, Belgium

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHU d'Angers

Angers, 49033, France

Location

CHU Hotel

Grenoble, 38043, France

Location

CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang

Lille, 59037, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU de Nice Archet I

Nice, 06202, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Centre hospitalier Lyon Sud Hematologie

Pierre-Bénite, 69495, France

Location

Hopital civil

Strasbourg, 67091, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31059, France

Location

Hopital Bretonneau

Tours, 37044, France

Location

Universitatsklinikum Bonn

Bonn, 53105, Germany

Location

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Marien Hospital

Düsseldorf, 40479, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo

Allessandria, 15100, Italy

Location

Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50121, Italy

Location

Azienda Sanitaria Locale Lecce

Lecce, 73100, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, 89100, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Roma, 00168, Italy

Location

Fondazione PTV Policlinico Tor Vergata

Roma, 00168, Italy

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, 2135, Netherlands

Location

Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitario Vall D hebron

Barcelona, 08035, Spain

Location

Instituto Catalan de Oncologia-Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Sahlgrenska Universitetssjukhus

Gothenburg, SE-41685, Sweden

Location

Skanes Universitetssjukhus Lund

Lund, 222 41, Sweden

Location

Karolinska University Hospital

Stockholm, SE-17176, Sweden

Location

Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Cukurova University Medical Faculty Balcali Hospital

Adana, 01330, Turkey (Türkiye)

Location

Ankara University Medical Faculty Cebeci Hospital

Ankara, 06590, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty Hospital

Istanbul, 34098, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, 35100, Turkey (Türkiye)

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

John Radcliffe Hospital

Headington, OX3 9DU, United Kingdom

Location

St James University Hospital

Leeds, LS1 3EX, United Kingdom

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Kings Mill Hospital

Sutton in Ashfield, NG17 4SL, United Kingdom

Location

Related Publications (6)

• Porter J. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.

  PMID: 30504333 BACKGROUND

• Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.

  PMID: 30617198 BACKGROUND

• Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.

  PMID: 31914241 RESULT

• Komrokji RS. Luspatercept in Myelodysplastic Syndromes: Who and When? Hematol Oncol Clin North Am. 2020 Apr;34(2):393-400. doi: 10.1016/j.hoc.2019.10.004. Epub 2020 Jan 21.

  PMID: 32089218 RESULT

• Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2.

  PMID: 30602619 RESULT

• Germing U, Fenaux P, Platzbecker U, Buckstein R, Santini V, Diez-Campelo M, Yucel A, Tang D, Fabre S, Zhang G, Zoffoli R, Ha X, Miteva D, Hughes C, Komrokji RS, Zeidan AM, Garcia-Manero G. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Ann Hematol. 2023 Feb;102(2):311-321. doi: 10.1007/s00277-022-05071-8. Epub 2023 Jan 13.

  PMID: 36635381 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Rodrigo Ito, MD

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2015
• First Posted: December 15, 2015
• Study Start: February 9, 2016
• Primary Completion: June 18, 2019
• Study Completion: November 26, 2020
• Last Updated: December 17, 2021
• Results First Posted: May 22, 2020

Record last verified: 2021-11

Locations

BE (7); CA (4); DE (6); ES (8); GB (6); SE (4); TU (4); FR (11); IT (8); US (13); NL (3)