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

Phase 3RecruitingNCT05949684

Bristol-Myers Squibb360 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

360

Conditions

Myelodysplastic Syndromes

Interventions

LuspaterceptBIOLOGICAL

Specified dose on specified days

Epoetin AlfaBIOLOGICAL

Specified dose on specified days

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 is erythropoiesis-stimulating agent naive. Participants may be randomized at the investigator's discretion if the participant received no more than 2 prior doses of epoetin alfa, epoetin alfa biosimilar, or darbepoetin alfa, with the last dose at least 8 weeks prior to randomization. * 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 baseline Hb concentration prior to randomization of ≤ 9.5 g/dL. The baseline Hb will be calculated using the mean of the two lowest available Hb measurements within 16 weeks prior to randomization and must include at least one central lab Hb reading done within the screening period (no more than 35 days before randomization). The two Hb measurements must have been performed at least seven days apart. Hb levels less than 21 days following RBC transfusion should not be used. Split samples for local assessments are not required. 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.

Locations (169)

Outcomes

Primary Outcomes

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.

Time frame: Up to Week 96

Secondary Outcomes

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

Time frame: Up to Week 48

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

Time frame: Up to Week 48

Time frame: From Week 49 to Week 96

Time frame: Up to Week 96

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

Time frame: Up to Week 48

Central Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286 Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Community Cancer Institute

Clovis, California, United States

RECRUITING

Compassionate Cancer Care Medical Group

Fountain Valley, California, United States

RECRUITING

Local Institution - 0095

Fresno, California, United States

WITHDRAWN

Cancer and Blood Specialty Clinic

Los Alamitos, California, United States

RECRUITING

UCLA Hematology/Oncology - Westwood (Building 200 Suite 120)

Los Angeles, California, United States

RECRUITING

St. Joseph Hospital

Orange, California, United States

RECRUITING

Ventura County Hematology Oncology Specialists

Oxnard, California, United States

RECRUITING

John Muir Health - Behring Pavilion

Walnut Creek, California, United States

RECRUITING

Local Institution - 0098

Fort Collins, Colorado, United States

WITHDRAWN

Hartford Hospital (HH)

Hartford, Connecticut, United States

RECRUITING

...and 159 more locations

Time frame: From Week 49 to Week 96

Time frame: Up to Week 96

Mean Hb change over fixed 24-week periods compared to the baseline Hb

Time frame: Baseline, Week 24, Week 48, Week 72, Week 96

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

Time frame: Up to Week 96

Number of participants with TD by week 48

Time frame: Up to Week 48

Time to TD (IWG 2018 defined as ≥ 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study

Time frame: Up to 5 years

Time from first Luspatercept dose to first RBC transfusion

Time frame: Up to 5 years

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

Time frame: Up to Week 48

Time frame: Up to Week 96

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)

Time frame: Up to Week 48

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)

Time frame: Up to Week 96

Number of participants with RBC transfusion independence over at least a consecutive 24-week period

Time frame: Up to 5 years

Number of transfusions

Time frame: Up to 5 years

Number of transfusions visits/units

Time frame: Up to 5 years

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)

Time frame: Baseline, Up to 5 years

Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L)

Time frame: Baseline, Up to 5 years

Number of participants with adverse events (AEs)

Time frame: Up to Week 102

Number of participants with antidrug antibody (ADA) (positive or negative)

Time frame: Up to Week 102

Pharmacokinetics (PK): Serum concentration

Time frame: Up to Week 96

PK: Area under the plasma concentration time curve (AUC)

Time frame: Up to Week 96

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.

Time frame: Up to Week 96

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.

Time frame: Up to Week 96

Number of participants with acute myeloid leukemia (AML) progression

Time frame: Up to 5 years

Time to AML progression

Time frame: Up to 5 years

Number of participants with high risk myelodysplastic syndromes (MDS) progression

Time frame: Up to 5 years

Time to high-risk MDS progression

Time frame: Up to 5 years

Time from date of randomization up to death due to any cause

Time frame: Up to 5 years