NCT03682536 · CITED IN SOURCE DOCUMENTS

A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2024-11-20

The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL

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outcome · POSTED

Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 Weeks

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outcome · POSTED

Mean Hemoglobin Change Over 24 Weeks

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outcome · POSTED

Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWG

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outcome · POSTED

Time to Hematologic Improvement - Erythroid Response (HI-E)

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outcome · POSTED

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)

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outcome · POSTED

Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)

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outcome · POSTED

Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)

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outcome · POSTED

Time to First Red Blood Cell (RBC) Transfusion

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outcome · POSTED

The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of Treatment

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outcome · POSTED

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)

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outcome · POSTED

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week Period

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outcome · POSTED

The Number of Participants With Acute Myeloid Leukemia (AML) Progression

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outcome · POSTED

Median Time to Acute Myeloid Leukemia (AML) Progression

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

The Number of Participants With Adverse Events (AEs)

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outcome · POSTED

Number of Participants With a Positive Anti-drug Antibody (ADA) Test

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outcome · POSTED

Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)

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outcome · POSTED

Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An)

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outcome · NOT POSTED

Area Under the Concentration-time Curve [AUC]

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outcome · NOT POSTED

Maximum Plasma Concentration of Drug [Cmax]

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Documented diagnosis of Myelodysplastic syndromes (MDS) according to WHO 2016 classification that meets revised international prognostic scoring system (IPSS-R) classification of very low, low, or intermediate risk disease, and have \< 5% blasts in bone marrow * Endogenous serum erythropoietin (sEPO) level of \< 500 U/L * Requires Red blood cell (RBC) transfusions, as documented by the criteria: Average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells (pRBCs) confirmed for a minimum of 8 weeks immediately preceding randomization * Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 Exclusion Criteria: * Clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any type of known clinically significant bleeding or sequestration or drug induced anemia * Known history of diagnosis of Acute myeloid leukemia (AML) * Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment Other protocol-defined inclusion/exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: Luspatercept
label
Luspatercept
type
EXPERIMENTAL
intervention Names
Drug: Epoetin alfa
label
Epoetin alfa
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Luspatercept
description
Specified dose on specified days
name
Luspatercept
other Names
ACE-536
type
DRUG
arm Group Labels
Epoetin alfa
description
Specified dose on specified days
name
Epoetin alfa
other Names
EPREX®
ERYPO®
PROCRIT®
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 363
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Percentage of participants who are RBC transfusion-free for any 12-week period associated with a concurrent mean hemoglobin (Hgb) increase ≥ 1.5 g/dL compared to baseline. After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated. 4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being \< 14 days after the previous transfusion.
measure
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL
time Frame
Week 1 through Week 24

secondary Outcomes

description
Red blood cell transfusion independence (RBC-TI) for 24 weeks is defined as the percentage of participants who did not receive RBC transfusions from Week 1 through Week 24.
measure
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 Weeks
time Frame
Week 1 through Week 24
description
Mean hemoglobin (Hgb) change over the 24-week period of Week 1 through Week 24 compared to baseline. After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated. 4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being \< 14 days after the previous transfusion.
measure
Mean Hemoglobin Change Over 24 Weeks
time Frame
Week 1 through Week 24
description
The percentage of participants meeting the modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of \>= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of \< 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.
measure
Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWG
time Frame
Week 1 through Week 24
description
Time from first dose to first onset of achieving modified HI-E. The modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of \>= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of \< 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.
measure
Time to Hematologic Improvement - Erythroid Response (HI-E)
time Frame
Week 1 through Week 24
description
Percentage of participants who are RBC transfusion-free over a consecutive 84-day period.
measure
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)
time Frame
Week 1 through Week 24
description
Maximum duration of RBC transfusion independence for participants who achieve RBC-TI ≥ 84 days.
measure
Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)
time Frame
Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
description
Time from first dose to first onset of transfusion independence ≥ 84 days.
measure
Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)
time Frame
Week 1 through Week 24
description
Time to first RBC transfusion is defined as time from Week 1 to first RBC transfusion on treatment. Participants who maintain RBC-TI through the end of the Treatment Period or time of analysis will be censored at EOT visit date, subsequent MDS therapy start date, study discontinuation date, analysis cutoff date or death, whichever occurs first. Median is from un-stratified Kaplan-Meier method.
measure
Time to First Red Blood Cell (RBC) Transfusion
time Frame
Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)
description
RBC transfusion burden on treatment is defined as total number of packed red blood cell (pRBC) units transfused within the first 24 weeks of treatment since Week 1.
measure
The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of Treatment
time Frame
Week 1 through Week 24
description
Defined as percentage of participants achieving RBC-TI for \>= 56 days during any consecutive 56-day period from Week 1 through Week 24.
measure
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)
time Frame
Week 1 through Week 24
description
Defined as percentage of participants achieving RBC-TI for \>= 168 days during any consecutive 168-day period from Week 1 through Week 48.
measure
Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week Period
time Frame
Week 1 through Week 48
description
Progression to AML is defined as a diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.
measure
The Number of Participants With Acute Myeloid Leukemia (AML) Progression
time Frame
From randomization to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)

Full study description

brief Summary: The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).

Source references

references

citation
Komrokji RS, Hayati S, Ugidos M, Garcia-Manero G, Della Porta MG, Zeidan AM, Santini V, Platzbecker U, Gandhi AK, Suragani RNVS. Impact of Mutational Landscape and Burden on RBC Transfusion Response in Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the COMMANDS Study. Am J Hematol. 2026 Mar;101(3):427-438. doi: 10.1002/ajh.70171. Epub 2026 Jan 19.
pmid
41549790
type
DERIVED
citation
Garcia-Manero G, Santini V, Zeidan AM, Komrokji RS, Pozharskaya V, Rose S, Keeperman K, Lai Y, Kalsekar S, Aggarwal B, Miteva D, Valcarcel D, Fenaux P, Shortt J, Della Porta MG, Platzbecker U. Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial. Adv Ther. 2025 Jul;42(7):3576-3589. doi: 10.1007/s12325-025-03208-5. Epub 2025 May 16.
pmid
40377899
type
DERIVED
citation
Della Porta MG, Garcia-Manero G, Santini V, Zeidan AM, Komrokji RS, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong IS, Lin CC, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman KL, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Sep;11(9):e646-e658. doi: 10.1016/S2352-3026(24)00203-5. Epub 2024 Jul 19.
pmid
39038479
type
DERIVED
citation
Platzbecker U, Della Porta MG, Santini V, Zeidan AM, Komrokji RS, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong IS, Lin CC, Li J, Zhang J, Giuseppi AC, Kreitz S, Pozharskaya V, Keeperman KL, Rose S, Shetty JK, Hayati S, Vodala S, Prebet T, Degulys A, Paolini S, Cluzeau T, Fenaux P, Garcia-Manero G. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023 Jul 29;402(10399):373-385. doi: 10.1016/S0140-6736(23)00874-7. Epub 2023 Jun 10.
pmid
37311468
type
DERIVED