A Study to Assess Luspatercept in Lower-risk Myelodysplastic Syndrome Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Luspatercept when administered at the maximum approved dose in low-risk Myelodysplastic Syndrome participants who require red blood cell transfusions.

Official Title
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A Phase 3b, Open-label Study Evaluating the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) Initiated at Maximum Approved Dose in LR-MDS With IPSS-R Very Low-, Low-, or Intermediate-risk Who Require RBC Transfusions (MAXILUS)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Luspatercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant had documented diagnosis of MDS according to World Health Organization (WHO) classification that met Revised International Prognostic Scoring System (IPSS-R) classification of very low-, low-, or intermediate-risk disease. Participant has an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. Participant must have red blood cell transfusions according to study criteria. Exclusion Criteria: Participant has known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. Participant has had a prior allogeneic or autologous stem cell transplant. Participant has known history or diagnosis of AML. Participant has uncontrolled hypertension. Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: erythropoiesis-stimulating agents (ESA) naïve<br> | Drug: Luspatercept<br>* Specified dose on specified days.<br>* Other names: REBLOZYL;|
| Experimental: Cohort 2: ESA relapsed or refractory<br> | Drug: Luspatercept<br>* Specified dose on specified days.<br>* Other names: REBLOZYL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieve red blood cell transfusion independence (RBC-TI) for 8 weeks with a simultaneous mean hemoglobin (Hb) increase of ≥ 1 g/dL from Week 1 to Week 24 |  | Up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with a mean change in total RBC units transfused over a fixed 16-week period from Week 9 to Week 24 and from Week 33 to Week 48 |  | Up to week 48 | 
| Number of participants who have a time from first dose to first onset of RBC-TI ≥ 8-, 12-, and 16-weeks from Week 1 to Week 24, from Week 1 to Week 48, and from Week 1 through EOT |  | Up to 2 years | 
| Number of participants who achieve RBC-TI over any consecutive 8-week period from Week 1 to Week 24, from Week 1 to Week 48, and from Week 1 to EOT |  | Up to 2 years | 
| Number of participants with a maximum duration of RBC-TI for participants who achieve RBC TI ≥ 8- and 16-week period from Week 1 to Week 24 and from Week 1 to EOT |  | Up to 2 years | 
| Number of participants who achieve RBC-TI over any consecutive 12-, 16-, and 24-week periods from Week 1 to Week 24, from Week 1 to Week 48 and from Week 1 through EOT |  | Up to 2 years | 
| Number of participants with an increase from baseline in mean hemoglobin (Hb) values of ≥ 1.0 g/dL over any consecutive 8-week period in absence of RBC transfusions from Week 1 to Week 48 and from Week 1 through EOT |  | Up to 2 years | 
| Number of participants with an increase from baseline in Hb values of ≥ 1.0 g/dL over any consecutive 16-week period in absence of RBC transfusions from Week 1 to Week 24, from Week 1 to Week 48, and from Week 1 through EOT |  | Up to 2 years | 
| Number of participants with an increase from baseline in Hb values of ≥ 1.5 g/dL over any consecutive 8-, and 16-week periods in absence of RBC transfusions from Week 1 to Week 24, from Week 1 to Week 48, and from Week 1 through EOT |  | Up to 2 years | 
| Number of participants who achieve Hematological Improvement Erythroid (mHI-E) per International Working Group-2018 (IWG-2018) over any consecutive 8-week period from Week 1 to Week 24, from Week 1 to Week 48, and Week 1 through EOT |  | Up to 2 years | 
| Number of participants who achieve Hematological Improvement - Neutrophils (HI-N) per IWG-2018 over any consecutive 8-week period from Week 1 to Week 24, from Week 1 to Week 48, and Week 1 through EOT |  | Up to 2 years | 
| Number of participants who achieve Hematological Improvement - Platelets (HI-P) per IWG-2018 over any consecutive 8-week period from Week 1 to Week 24, from Week 1 to Week 48, and Week 1 through EOT |  | Up to 2 years | 
| Number of participants with change in serum ferritin (SF) over a 16-week period from Week 9 to Week 24 and from Week 33 to Week 48 |  | Up to week 48 | 
| Number of participants with change in mean daily dose of iron chelation therapy (ICT) over a 16-week period from Week 9 to Week 24 and from Week 33 to Week 48 |  | Up to week 48 | 
| Number of participants with adverse events (AEs) |  | Up to 2 years | 
| Number of participants with acute myeloid leukemia (AML) progression |  | Up to 4 years | 
| Time to AML progression |  | Up to 4 years | 
| Time from treatment start date to death due to any cause |  | Up to 4 years | 
| Number of participants with a change in subscale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) from Week 1 to Week 48 and from baseline through EOT |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Luspatercept, Transfusion dependent, ACE-536, Anemia, Blood Transfusion, Red Blood Cell Transfusion, Myelodysplastic Syndrome