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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05949684
• Collaborator: (none)
• Enrollment: 360
• Locations: 101
• Arms: 2
• Anticipated Duration (Months): 78.9
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Biological: Luspatercept; Biological: Epoetin Alfa	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Aug 15, 2023
• Anticipated Primary Completion Date: Jun 25, 2027
• Anticipated Study Completion Date: Mar 11, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Luspatercept	Biological: Luspatercept; Specified dose on specified days; Other Names: BMS-986346 ACE-536 Reblozyl®
Active Comparator: Epoetin Alfa	Biological: Epoetin Alfa; Specified dose on specified days; Other Names: Epogen® PROCRIT® BINOCRIT

Outcome Measures

Primary Outcome Measures

1. 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 [Up to Week 96]

   TD is defined as ≥ 3 red blood cells (RBC) units/16 weeks assessed by International Working Group (IWG) 2018.

Secondary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. Mean Hb change over fixed 24-week periods compared to the baseline Hb [Baseline, Week 24, Week 48, Week 72, Week 96]

9. 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]

10. Number of participants with TD by week 48 [Up to Week 48]

11. 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]

12. Time from first Luspatercept dose to first RBC transfusion [Up to 5 years]

13. 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]

14. 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]

15. 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]

16. 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]

17. Number of participants with RBC transfusion independence over at least a consecutive 24-week period [Up to 5 years]

18. Number of transfusions [Up to 5 years]

19. Number of transfusions visits/units [Up to 5 years]

20. 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]

21. 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]

22. Number of participants with adverse events (AEs) [Up to Week 102]

23. Number of participants with antidrug antibody (ADA) (positive or negative) [Up to Week 102]

24. Pharmacokinetics (PK): Serum concentration [Up to Week 96]

25. PK: Area under the plasma concentration time curve (AUC) [Up to Week 96]

26. Number of participants with a platelet response at Week 24, Week 48 and Week 96 [Up to 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.

27. Number of participants with a neutrophil response at Week 24, Week 48 and Week 96 [Up to 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.

28. Number of participants with acute myeloid leukemia (AML) progression [Up to 5 years]

29. Time to AML progression [Up to 5 years]

30. Number of participants with high risk myelodysplastic syndromes (MDS) progression [Up to 5 years]

31. Time to high-risk MDS progression [Up to 5 years]

32. Time from date of randomization up to death due to any cause [Up to 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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.

Note: Other protocol-defined inclusion/exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Muir Medical Center - Concord Campus	Concord	California	United States	94520
2	Compassionate Cancer Care Medical Group	Fountain Valley	California	United States	92708
3	Ventura County Hematology Oncology Specialists	Oxnard	California	United States	93030
4	Innovative Clinical Research Institute	Whittier	California	United States	90603
5	Florida Cancer Specialists - South	Fort Myers	Florida	United States	33901
6	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
7	NAPA Research	Pompano Beach	Florida	United States	33064
8	Florida Cancer Specialists - North	Saint Petersburg	Florida	United States	33705
9	Hematology/Oncology of the North Shore	Skokie	Illinois	United States	60076
10	Orchard Healthcare Research Inc.	Skokie	Illinois	United States	60077
11	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
12	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico	United States	87131
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
15	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
16	Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
17	Mays Cancer Center	San Antonio	Texas	United States	78229
18	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
19	Fred Hutchinson Cancer Center at University of Washington Medical Center - Northwest	Seattle	Washington	United States	98133
20	Local Institution - 0012	Buenos Aires		Argentina	CP1280AEB
21	Local Institution - 0009	Ciudad Autónoma de Buenos Aires		Argentina	C1426ANZ
22	Local Institution - 0071	Blacktown	New South Wales	Australia	2148
23	Local Institution - 0113	Camperdown	New South Wales	Australia	2050
24	Local Institution - 0054	Clayton	Victoria	Australia	3168
25	Local Institution - 0052	Heidelberg	Victoria	Australia	3084
26	Local Institution - 0059	Fortaleza	Ceará	Brazil	60430-270
27	Local Institution - 0101	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
28	Local Institution - 0056	Rio de Janeiro		Brazil	20211-030
29	Local Institution - 0003	São Paulo		Brazil	05403-000
30	Local Institution - 0049	Calgary	Alberta	Canada	T2N 4N2
31	Local Institution - 0050	London	Ontario	Canada	N6A 5W9
32	Local Institution - 0017	Toronto	Ontario	Canada	M4N 3M5
33	Local Institution - 0109	Hefei	Anhui	China	230071
34	Local Institution - 0217	Beijing	Beijing	China	100034
35	Local Institution - 0030	Beijing	Beijing	China	100730
36	Local Institution - 0096	Fuzhou Fujian	Fujian	China	350001
37	Local Institution - 0220	Xiamen	Fujian	China	361003
38	Local Institution - 0031	Guangzhou	Guangdong	China	450008
39	Local Institution - 0221	Guangzhou	Guangdong	China	510630
40	Local Institution - 0038	Harbin	Heilongjiang	China	150010
41	Local Institution - 0194	Zhengzhou	Henan	China	450003
42	Local Institution - 0108	Wuhan	Hubei	China	430058
43	Local Institution - 0089	Changsha	Hunan	China	410008
44	Local Institution - 0032	Nanjing	Jiangsu	China	210029
45	Local Institution - 0079	Nanchang	Jiangxi	China	330006
46	Local Institution - 0043	Changchun	Jilin	China	130021
47	Local Institution - 0048	Shenyang	Liaoning	China	110001
48	Local Institution - 0216	Xian	Shaanxi	China	710068
49	Local Institution - 0111	Qingdao	Shandong	China	266003
50	Local Institution - 0218	Shanghai	Shanghai	China	200030
51	Local Institution - 0075	Cheng Du	Sichuan	China	610041
52	Local Institution - 0103	Tianjin	Tianjin	China	300020
53	Local Institution - 0029	Hangzhou	Zhejiang	China	310003
54	Local Institution - 0033	Wenzhou	Zhejiang	China	32500
55	Local Institution - 0147	Medellin	Antioquia	Colombia	05034
56	Local Institution - 0152	Valledupar	Cesar	Colombia	200001
57	Local Institution - 0149	Montería	Córdoba	Colombia	230002
58	Centre Hospitalier Universitaire de Nice - Hôpital l'Archet	Nice	Alpes-Maritimes	France	06202
59	CHU Bordeaux Haut-Leveque	Pessac	Aquitaine	France	33600
60	Chu Grenoble Alpes	La Tronche	Isère	France	38700
61	Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois	Vandoeuvre lès Nancy	Lorraine	France	54511
62	Hôpital Saint-Louis	Paris		France	75010
63	Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE	Toulouse		France	31100
64	Local Institution - 0168	Koblenz	Rheinland-Pfalz	Germany	56068
65	Local Institution - 0171	Leipzig	Sachsen	Germany	04103
66	Local Institution - 0169	Berlin		Germany	10117
67	Local Institution - 0028	Berlin		Germany	14195
68	Local Institution - 0207	Düsseldorf		Germany	40225
69	Local Institution - 0167	Mutlangen		Germany	73557
70	Local Institution - 0166	Würzburg		Germany	97080
71	Local Institution - 0132	Patras	Achaḯa	Greece	26504
72	Local Institution - 0084	Athens	Attikí	Greece	115 27
73	Local Institution - 0131	Chaidari	Attikí	Greece	12462
74	Local Institution - 0082	Alexandroupolis		Greece	08100
75	Local Institution - 0024	Eger	Heves	Hungary	0
76	Local Institution - 0021	Nyiregyhaza	Szabolcs-Szatmár-Bereg	Hungary	4400
77	Local Institution - 0026	Budapest		Hungary	1088
78	Local Institution - 0193	New Delhi	Delhi	India	110029
79	Local Institution - 0178	Bhubaneswar	Odisha	India	751003
80	Local Institution - 0185	Hyderabad		India	500034
81	Local Institution - 0137	Milano	Lombardia	Italy	20122
82	Local Institution - 0134	Milan	Milano	Italy	20162
83	Local Institution - 0136	Rozzano	Milano	Italy	20089
84	Local Institution - 0138	Firenze	Toscana	Italy	50134
85	Local Institution - 0135	Bologna		Italy	40138
86	Local Institution - 0076	Reggio Calabria		Italy	89125
87	Local Institution - 0085	Torino		Italy	10128
88	Local Institution - 0133	Verona		Italy	37134
89	Local Institution - 0142	Mexico City	Distrito Federal	Mexico	14080
90	Local Institution - 0069	Huixquilucan		Mexico	52787
91	Local Institution - 0150	Puebla		Mexico	72424
92	Local Institution - 0130	Wałbrzych	Dolnośląskie	Poland	58-309
93	Local Institution - 0062	Warsaw	Mazowieckie	Poland	02-106
94	Local Institution - 0060	Gdańsk	Pomorskie	Poland	80-952
95	Local Institution - 0061	Katowice		Poland	40-519
96	Auxilio Mutuo Cancer Center	San Juan		Puerto Rico	00917
97	Local Institution - 0198	Barcelona	Barcelona [Barcelona]	Spain	08035
98	Local Institution - 0197	L'Hospitalet de Llobregat	Catalunya [Cataluña]	Spain	08908
99	Local Institution - 0196	Valencia	Valenciana, Comunitat	Spain	46010
100	Local Institution - 0199	Granada		Spain	18012
101	Local Institution - 0200	Salamanca		Spain	37007

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT05949684
• Other Study ID Numbers: CA056-025; 2022-500430-29-00
• First Posted: Jul 18, 2023
• Last Update Posted: Jul 21, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bristol-Myers Squibb: Luspatercept; BMS-986346; ACE-536; Myelodysplastic Syndrome; Epoetin alfa; Erythropoietin stimulating agent (ESA); Myelodysplastic Syndromes (MDS); Anaemia
• Additional relevant MeSH terms: Preleukemia; Anemia; Myelodysplastic Syndromes; Syndrome; Epoetin Alfa; Luspatercept

Study Results

No Results Posted as of Jul 21, 2023