ELEMENT-MDS: A Study to Compare the Efficacy and Safety of Luspatercept in Participants With Myelodysplastic Syndrome (MDS) and Anemia Not Receiving Blood Transfusions

Myelodysplastic Syndromes Clinical Trial

— ELEMENT-MDS  

Official title:

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) vs Epoetin Alfa for the Treatment of Anemia Due to Revised International Prognostic Scoring System (IPSS-R) Very Low, Low, or Intermediate-Risk Myelodysplastic Syndrome (MDS) in Erythropoiesis-Stimulating Agent (ESA)-Naive Participants Who Are Non-Transfusion Dependent (NTD): The "ELEMENT-MDS" Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05949684
• Other study ID #: CA056-025
• Secondary ID: 2022-500430-29-0
• Status: Recruiting
• Phase: Phase 3
• Start date: October 24, 2023
• Est. completion date: March 11, 2030

Study information

• Verified date: June 2024
• Source: Bristol-Myers Squibb
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare the efficacy and safety of Luspatercept vs epoetin alfa in the treatment of anemia in adults due to IPSS-R very low, low, intermediate-risk MDS in ESA-naïve participants who are non-transfusion dependent (NTD).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: March 11, 2030
• Est. primary completion date: June 25, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Participant has documented diagnosis of MDS according to World Health Organization (WHO) 2016 that meet IPSS-R classification of very low, low, or intermediate-risk disease, (intermediate-risk of = 3.5 IPSS-R score) confirmed via bone marrow aspirate and:.

i) < 5% blasts in bone marrow and < 1% blasts in peripheral blood.

• Participant is not transfusion dependent (NTD) based on IWG2018 criteria.

• Participant has never received treatment with an erythropoiesis stimulating agent (ESA).

• Participant has a baseline endogenous serum erythropoietin (sEPO) level of = 500 U/L.

• Participant has symptoms of anemia:.

i) Participant records a severity score of "moderate" or greater on at least 1 PGI-S item of fatigue, weakness, shortness of breath, or dizziness performed during the screening period.

• Participant has a mean baseline Hb concentration prior to randomization of = 9.5 g/dL. Mean Hb is defined as the mean of all central/ local/ pretransfusion available Hb measurements during the 16 weeks prior to randomization (with a minimum of 2 measurements at least 1 week apart). Only Hb levels > 21 days following a transfusion are acceptable. The last measurement must be within 35 days of randomization.

Exclusion Criteria

• Participant with secondary MDS (that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).

• Participant with known history of diagnosis of AML.

• Participant with history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis within 6 months prior to randomization.

• Participant with a history of pure red cell aplasia and/or antibody against erythropoietin.

• Other protocol-defined Inclusion/Exclusion criteria apply.

Related Conditions & MeSH terms

• Anemia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• Luspatercept
Specified dose on specified days
• Epoetin Alfa
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Centro Mdico "Barrio Parque"	Buenos Aires
Argentina	Local Institution - 0012	Buenos Aires
Argentina	Local Institution - 0009	Ciudad Autónoma de Buenos Aires
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Health	Clayton	Victoria
Australia	Local Institution - 0254	Coffs Harbour	New South Wales
Australia	Local Institution - 0246	Gold Coast	Queensland
Australia	Austin Health	Heidelberg	Victoria
Brazil	Hospital Universitario Walter Cantidio	Fortaleza	Ceará
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	HEMORIO	Rio de Janeiro
Brazil	Hospital das Clinicas FMUSP	São Paulo
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Victoria Hospital & Children's Hospital - London Health Sciences Centre	London	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Local Institution - 0112	Vancouver	British Columbia
China	Beijing Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital Central South University	Changsha	Hunan
China	West China Hospital of Sichuan University	Cheng Du	Sichuan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Local Institution - 0096	Fuzhou Fujian	Fujian
China	Local Institution - 0031	Guangzhou	Guangdong
China	The first Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Hospital of Harbin	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Local Institution - 0218	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Institute of hematology&blood disease hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated hospital of Xiamen University	Xiamen	Fujian
China	Shaanxi provincial people's hospital	Xian	Shaanxi
China	People's Hospital of Henan Province	Zhengzhou	Henan
Colombia	Local Institution - 0147	Medellin	Antioquia
Colombia	Local Institution - 0149	Montería	Córdoba
Colombia	Local Institution - 0152	Valledupar	Cesar
Czechia	Local Institution - 0080	Brno	Brno-mesto
Czechia	Fakultni nemocnice Ostrava	Ostrava	Moravskoslezský Kraj
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Chu Grenoble Alpes	La Tronche	Isère
France	Centre Hospitalier Universitaire de Nice - Hôpital l'Archet	Nice	Alpes-Maritimes
France	Hôpital Saint-Louis	Paris
France	CHU Bordeaux Haut-Leveque	Pessac	Aquitaine
France	Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE	Toulouse
France	Local Institution - 0019	Tours	Indre-et-Loire
France	Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois	Vandoeuvre lès Nancy	Lorraine
France	Local Institution - 0248	Villejuif	Val-de-Marne
Germany	Local Institution - 0028	Berlin
Germany	Praxis fur Hamatologie und Onkologie	Berlin
Germany	Universitaetsklinikum Duesseldorf	Düsseldorf
Germany	Local Institution - 0261	Erding	Bayern
Germany	Local Institution - 0251	Jena	Thüringen
Germany	Local Institution - 0250	Kempten	Bayern
Germany	Local Institution - 0168	Koblenz	Rheinland-Pfalz
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Local Institution - 0255	Lübeck
Germany	Local Institution - 0259	Münster	Nordrhein-Westfalen
Germany	Kliniken Ostalb, Stauferklinikum	Mutlangen
Germany	Gemeinschaftspraxis Dr. med. Björn Schöttker & Dominik Pretscher	Würzburg
Greece	University Hospital of Alexandroupolis	Alexandroupolis
Greece	General Hospital of Athens "G. Gennimatas"	Athens	Attikí
Greece	Attikon General University Hospital	Chaidari	Attikí
Greece	Local Institution - 0132	Patras	Acha?a
Greece	Local Institution - 0242	Patras	Acha?a
Hungary	Semmelweis Egyetem	Budapest
Hungary	Heves Vármegyei Markhot Ferenc Oktatókórház és Rendelointézet	Eger	Heves
Hungary	Szabolcs Szatmár Bereg Vármegyei Oktatókórház	Nyiregyhaza	Szabolcs-Szatmár-Bereg
India	Local Institution - 0243	Ahmedabad	Gujarat
India	Local Institution - 0177	Bengaluru	Karnataka
India	Local Institution - 0178	Bhubaneswar	Odisha
India	Local Institution - 0185	Hyderabad
India	Local Institution - 0186	New Delhi
India	Local Institution - 0193	New Delhi	Delhi
India	Local Institution - 0235	New Delhi	Delhi
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola	Bologna
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan	Milano
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Local Institution - 0076	Reggio Calabria
Italy	Local Institution - 0244	Roma
Italy	Local Institution - 0256	Rome	Lazio
Italy	Humanitas	Rozzano	Milano
Italy	Azienda Ospedaliera Ordine Mauriziano di Torino	Torino	Piemonte
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma	Verona
Mexico	Hematológica Alta Especialidad SC, consultorio 830	Huixquilucan
Mexico	Local Institution - 0142	Mexico City	Distrito Federal
Mexico	Unidad Médica Onco-hematológica	Puebla
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Pratia Onkologia Katowice	Katowice
Poland	Specjalistyczny Szpital im. dra Alfreda Sokolowskiego w Walbrzychu	Walbrzych	Dolnoslaskie
Poland	MTZ Clinical Research powered by Pratia	Warsaw
Puerto Rico	Auxilio Mutuo Cancer Center	San Juan
Puerto Rico	Local Institution - 0237	San Juan
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Local Institution - 0199	Granada
Spain	Institut Català d'Oncologia - L'Hospitalet	L'Hospitalet de Llobregat	Catalunya [Cataluña]
Spain	Local Institution - 0252	Madrid
Spain	Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca	Salamanca
Spain	Hospital Clinico de Valencia	Valencia	Valenciana, Comunitat
United States	Our Lady of the Lake RMC	Baton Rouge	Louisiana
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	Community Cancer Institute	Clovis	California
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	John Muir Medical Center - Concord Campus	Concord	California
United States	Pontchartrain Cancer Center	Covington	Louisiana
United States	Halifax Health Medical Center	Daytona Beach	Florida
United States	Local Institution - 0230	Daytona Beach	Florida
United States	Local Institution - 0098	Fort Collins	Colorado
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Compassionate Cancer Care Medical Group	Fountain Valley	California
United States	Local Institution - 0095	Fresno	California
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Hartford Hospital (HH)	Hartford	Connecticut
United States	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi
United States	Local Institution - 0240	Honolulu	Hawaii
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	D&H Cancer Research Center LLC	Margate	Florida
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	Local Institution - 0097	New Orleans	Louisiana
United States	Local Institution - 0247	Orange	California
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Local Institution - 0232	Pikeville	Kentucky
United States	BRCR Global	Plantation	Florida
United States	Local Institution - 0236	Richmond	Virginia
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Metro-Minnesota Community Clinical Oncology	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists - North	Saint Petersburg	Florida
United States	Local Institution - 0213	Seattle	Washington
United States	Orchard Healthcare Research Inc.	Skokie	Illinois
United States	Local Institution - 0238	Tamarac	Florida
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Mexico,  Poland,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with lower-risk non-transfusion dependent myelodysplastic syndromes (NTD-MDS) who converted to Transfusion Dependence (TD) during any continuous 16-week interval within the 96-week treatment period	TD is defined as = 3 red blood cells (RBC) units/16 weeks assessed by International Working Group (IWG) 2018.	Up to Week 96
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.5 grams/deciliter (g/dL) in any continuous 16-week interval within the 48 week Treatment Period in the absence of transfusion		Up to Week 48
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 48
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		From Week 49 to Week 96
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 96
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 48
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		From Week 49 to Week 96
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion		Up to Week 96
Secondary	Mean Hb change over fixed 24-week periods compared to the baseline Hb		Baseline, Week 24, Week 48, Week 72, Week 96
Secondary	Number of participants with an increase from baseline in mean Hb values of = 1.5 g/dL in any continuous 16-week interval within the 96-week treatment period in the absence of transfusion		Up to Week 96
Secondary	Number of participants with TD by week 48		Up to Week 48
Secondary	Time to TD (IWG 2018 defined as = 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study		Up to 5 years
Secondary	Time from first Luspatercept dose to first RBC transfusion		Up to 5 years
Secondary	Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of =1.5g/dL in any continuous 16-week interval within 48-week treatment period in absence of transfusion		Up to Week 48
Secondary	Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of =1.5g/dL in any continuous 16-week interval within 96-week treatment period in absence of transfusion		Up to Week 96
Secondary	Time from first dose to first day of response (increase in mean Hb values of = 1.5 g/dL in any continuous 16-week interval within the 48-week Treatment Period in the absence of transfusion)		Up to Week 48
Secondary	Time from first dose to first day of response (increase in mean Hb values of = 1.5 g/dL in any continuous 16-week interval within the 96-week Treatment Period in the absence of transfusion)		Up to Week 96
Secondary	Number of participants with RBC transfusion independence over at least a consecutive 24-week period		Up to 5 years
Secondary	Number of transfusions		Up to 5 years
Secondary	Number of transfusions visits/units		Up to 5 years
Secondary	Change from baseline in subscales of self-reported health-related quality-of-life (HRQoL) assessed by the Functional Assessment of Cancer Therapy - Anemia (FACT-An)		Baseline, Up to 5 years
Secondary	Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L)		Baseline, Up to 5 years
Secondary	Number of participants with adverse events (AEs)		Up to Week 102
Secondary	Number of participants with antidrug antibody (ADA) (positive or negative)		Up to Week 102
Secondary	Pharmacokinetics (PK): Serum concentration		Up to Week 96
Secondary	PK: Area under the plasma concentration time curve (AUC)		Up to Week 96
Secondary	Number of participants with a platelet response at Week 24, Week 48 and Week 96	Platelet response is defined as an increase from baseline in number of platelets to = 30 × 10^9/L at Week 24, Week 48 and Week 96.	Up to Week 96
Secondary	Number of participants with a neutrophil response at Week 24, Week 48 and Week 96	Neutrophil response is defined as an absolute increase from baseline of > 0.5 × 10^9/L neutrophils at Week 24, Week 48 and Week 96.	Up to Week 96
Secondary	Number of participants with acute myeloid leukemia (AML) progression		Up to 5 years
Secondary	Time to AML progression		Up to 5 years
Secondary	Number of participants with high risk myelodysplastic syndromes (MDS) progression		Up to 5 years
Secondary	Time to high-risk MDS progression		Up to 5 years
Secondary	Time from date of randomization up to death due to any cause		Up to 5 years

External Links

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