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Myelodysplastic SyndromesPhase 3LUSPLUSNCT05181592

Assessment of Effectiveness and Safety of Luspatercept in Patients Suffering From Lower-risk Myelodysplastic Syndrome.

A Phase 3 study testing Luspatercept in people with Myelodysplastic Syndromes, run by GWT-TUD GmbH at 13 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

A phase IIIb, open-label, single arm study to evaluate the efficacy and safety of luspatercept in patients with lower-risk MDS and ring-sideroblastic phenotype (MDS-RS) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Luspatercept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
13 sitesin 4 countries
Study dates
27 Oct 2021to 28 Feb 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject is 18 years of age or older at the time of signing the informed consent form (ICF)
  • Subject is able to understand and voluntarily sign the ICF prior to any study-related assessments/procedures being conducted
  • Subject has documented diagnosis of MDS according to WHO classification that meets IPSS-R classification[3] of very low-, low-, or intermediate-risk disease, and the following:
  • Ring sideroblasts (RS) ≥ 15% of erythroid precursors in bone marrow or ≥ 5% if SF3B1 mutation is present
  • Less than 5% blasts in bone marrow
  • Peripheral blood white blood cell (WBC) count < 13,000/μL
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  • Subject must be one of the following:
  • Refractory to prior ESA treatment: Documentation of non-response or response that was no longer maintained to prior ESA-containing regimen, either as a single agent or in combination (e.g. with granulocyte colony-stimulating factor [G-CSF]). The ESA regimen must be either:
  • Recombinant human erythropoietin ≥ 40,000 IU/week for at least 8 weeks (=doses) or equivalent; or
  • Darbepoetin-α ≥ 500 μg q3w for at least 4 doses or equivalent
  • Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA containing regimen, either as a single agent or in combination (e.g. with G-CSF), at any time after introduction due to intolerance or an adverse event (AE)
  • ESA ineligible: Low chance of response to ESA based on endogenous serum erythropoietin (EPO) level > 200 U/L for subjects not previously treated with ESAs
  • Refractory to- /relapsed after prior HMA treatment1: Treatment failure/relapse after at least six (azacitidine) or four (decitabine) 4-week treatment cycles except for del(5q) MDS
  • Refractory to- /relapsed after prior lenalidomide treatment1 except for del(5q) MDS
  • If previously treated with ESAs or G-CSF/granulocyte-macrophage colony-stimulating factor (GM-CSF), both agents must be discontinued ≥ 4 weeks prior to the date of starting treatment with the Investigational medicinal Product (IMP) in this study
  • Required RBC transfusions, as documented by the following criteria:
  • Average transfusion requirement of ≥ 2 units/8 weeks of packed RBCs confirmed for a minimum period of 16 weeks immediately preceding start of treatment with IMP
  • Hemoglobin (Hb) levels at the time of or within 7 days prior to administration of an RBC transfusion must be ≤ 10.0 g/dL in order for the transfusion to be counted towards meeting eligibility criteria. RBC transfusions administered when Hb levels are > 10 g/dL and/or RBC transfusions administered for elective surgery do not qualify as a required transfusion for the purpose of meeting eligibility criteria
  • No consecutive 56-day period that is RBC transfusion-free during the 16 weeks immediately prior to starting treatment with IMP
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
  • A female of childbearing potential (FCBP) for this study is defined as a sexually mature woman who: (1) has not undergone a hysterectomy or bilateral oophorectomy; or (2) is not naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e. had menses at any time in the preceding 24 consecutive months). An FCBP participating in the study must:
  • Have 2 negative pregnancy tests as verified by the investigator prior to starting IMP (unless the screening pregnancy test is done within 72 hours of Cycle 1 Day 1). She must agree to ongoing pregnancy testing during the course of the study and after end of treatment (EOT).
  • If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting IMP, during treatment with IMP (including dose interruptions), and for 12 weeks after discontinuation of IMP. Highly effective contraception is defined in this protocol as the following (information also appears in the ICF): Hormonal contraception (e.g. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation, or a partner with a vasectomy
  • Male subjects must agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g. polyurethane), during sexual contact with a pregnant female or an FCBP while participating in the study, during dose interruptions, and for at least 12 weeks following IMP discontinuation, even if he has undergone a successful vasectomy
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements

Who cannot join

  • Prior therapy with disease modifying agents other than HMA or LEN for underlying MDS disease
  • Previously treated with either luspatercept or sotatercept
  • Secondary MDS, i.e. MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
  • Iron deficiency to be determined by local laboratory via serum ferritin ≤ 15 μg/L and additional testing if clinically indicated (e.g. calculated transferrin saturation [iron/total iron binding capacity ≤ 20%] or bone marrow aspirate stain for iron)
  • Prior allogeneic or autologous stem cell transplant
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  • Known history of diagnosis of acute myeloid leukemia (AML)
  • Use of any of the following within 5 weeks prior to the first dose of the IMP in this study:
  • Anticancer cytotoxic chemotherapeutic agent or treatment
  • Corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to the first dose of IMP for medical conditions other than MDS ICT, except for subjects on a stable or decreasing dose for at least 8 weeks prior to the first dose of IMP
  • Other RBC hematopoietic growth factors (e.g. interleukin [IL]-3)
  • Investigational drug or device, or approved therapy for investigational use. If the half-life of the previous study drug is known, the use of it within 5 times the half-life prior to the first dose of IMP or within 5 weeks, whichever is longer, is excluded
  • Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment
  • Platelet count < 30,000/μL (30 × 109/L)
  • Estimated glomerular filtration rate or creatinine clearance < 40 mL/min
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≥ 3.0 × upper limit of normal (ULN)
  • Total bilirubin ≥ 2.0 × ULN
  • Higher levels are acceptable if these can be attributed to active RBC precursor destruction within the bone marrow (i.e. ineffective erythropoiesis) or in the presence of known history of Gilbert Syndrome
  • Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs test or over 50% indirect bilirubin
  • Prior history of malignancies, other than MDS, unless the subject is free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
  • Basal or squamous cell carcinoma of the skin
  • Carcinoma in situ of the cervix
  • Carcinoma in situ of the breast
  • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system)
  • Major surgery within 8 weeks prior to the first dose of IMP. Subjects must be completely recovered from any previous surgery prior to the first dose of IMP
  • History of stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to the first dose of IMP
  • Pregnant or breast-feeding females
  • Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator within 6 months prior to the first dose of IMP. Subjects with a known ejection fraction of ˂ 35%, confirmed by a local echocardiography or multigated acquisition scan (MUGA) performed within 6 months prior to the first dose of IMP, are excluded
  • Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment), known human immunodeficiency virus (HIV), known evidence of active infectious hepatitis B, and/or known evidence of active hepatitis C
  • History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the IMP
  • Subject is in custody by order of an authority or a court of law
  • Participation in another interventional clinical study within the last 3 months prior to signing the ICF or simultaneous participation in other clinical studies
  • Close affiliation with the investigator (e.g. a close relative) or persons working at the study site
  • Subject is an employee of the sponsor or involved Contract research Organization (CRO)
  • Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Spain6 sites

  • Institut Català d' Oncologia de Badalona

    Badalona, 8916

  • Hospital Vall d´Hebron

    Barcelona, 08023

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28009

  • Hospital Universitario Central de Asturias

    Oviedo, 33011

  • University Hospital of Salamanca

    Salamanca, 37007

  • Hospital Universitario y Politecnico La Fe de Valencia

    Valencia, 46026

Other trials in Spain

Switzerland3 sites

  • Universitätsspital Basel

    Basel, 4031

  • Clinica di Ematologia Istituto oncologico della Svizzera Italiana

    Bellinzona, 6500

  • Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor

    Bern, 3010

Other trials in Switzerland

Austria2 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

Germany2 sites

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Klinikum rechts der Isar

    München, 81675

Other trials in Germany

About this study

Official title: A Phase IIIb, Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Luspatercept in Patients With Lower-risk MDS and Ring-sideroblastic Phenotype (MDS-RS)

A phase IIIb, open-label, single arm study to evaluate the efficacy and safety of luspatercept in patients with lower-risk MDS and ring-sideroblastic phenotype (MDS-RS)

Read the detailed description

This is a phase IIIb, single arm, multicenter study to further explore the efficacy and safety of luspatercept in subjects with anemia due to IPSS-R very low-, low-, or intermediate-risk MDS with RS who require RBC transfusions. The study will consist of a screening period, a treatment period (primary phase and extension phase), and a posttreatment follow-up period.

The study will involve study sites in Germany, France, Austria and Switzerland. It is planned to include 70 patients to receive treatment with luspatercept to end up with 64 evaluable subjects.

Being tested
Luspatercept
Keywords
MDS, Luspatercept, myelodysplastic syndrome, ring-sideroblastic phenotype, MDS-RS
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LuspaterceptDrug

    Also called Reblozyl

    Once 1.75 mg/kg on Day 1 of each 21-day cycle for 24 weeks (9 cycles)

Study groups in NCT05181592
Study groupRoleWhat they receive
Luspatercept (single arm)Experimentalopen-label, single-arm
Receives: Drug: Luspatercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. RBC-TI rate according to IWG 2018 modified criteria

    Evaluation of RBC-TI rate of luspatercept for the treatment of anemia due to IPSS-R very low-, low-, or intermediate-risk MDS in subjects with ring sideroblasts (RS) who require RBC transfusions (according to IWG 2018 criteria).

    Measured: from Week 1 through Week 24

Secondary outcomes (14)

  1. RBC-TI rate according to IWG 2006 criteria

    RBC-TI rates according to IWG 2006 criteria (Weeks 1-24 and Weeks 1-52) will be estimated and 97.5% lower confidence limit will be calculated analogously to the primary endpoint.

    Measured: from Week 1 through Week 24 and through Week 52

  2. Median time to RBC-TI

    Time to RBC-TI will be summarized only for subjects who achieve RBC TI ≥ 8 weeks on treatment. It is defined as the time between start of IMP and the date onset of TI is first observed (i.e, Day 1 of 56 days without any RBC transfusions).

    Measured: Week 1 through Week 24 and through Week 52

  3. Median Duration of RBC-TI

    Duration of RBC-TI will be determined only for subjects who achieve RBC TI ≥ 8 weeks on treatment. Duration of RBC-TI is defined as the longest RBC-TI period during the treatment period. Duration of response starts at the date onset of TI is first observed (i.e, Day 1 of 56 days without any RBC transfusions). Transfusion response ends on the day of the first transfusion given after response is documented. Subjects who maintain RBC-TI through EOT will be censored at the date of treatment discontinuation or death, whichever occurs first.

    Measured: Week 1 through Week 24 and through Week 52

  4. Change in RBC units transfused

    Total number of RBC units transfused over a fixed 16-weeks period (weeks 9-24; weeks 37-52) will be compared to the total number of RBC units transfused in the 16 weeks immediately prior to first IMP.

    Measured: Week 9 through Week 24 and Week 37 through Week 52

  5. Proportion of subjects achieving mean Hb increase ≥ 1.0 g/dL

    Hemoglobin (Hb) increase ≥ 1.0 g/dL is defined as proportion of subjects with ≥ 1.0 g/dL Hb increase compared to baseline that is sustained over any consecutive 56-day period within a specified timeframe in the absence of RBC transfusions.

    Measured: Week 1 through Week 24 and through Week 52

  6. Proportion of subjects achieving modified hematologic improvement - erythroids (mHI-E) per IWG 2006 criteria

    Measured: Week 1 through Week 24 and through Week 52

  7. Proportion of subjects achieving hematologic improvement - neutrophils (HI-N) per IWG 2006 criteria

    Measured: Week 1 through Week 24 and through Week 52

  8. Proportion of subjects achieving hematologic improvement - platelets (HI-P) per IWG 2006 criteria

    Measured: Week 1 through Week 24 and through Week 52

  9. Mean change in serum ferritin

    Mean change in serum ferritin (Week 9-24; Weeks 37-52) is calculated as the difference of post-baseline mean serum ferritin and baseline mean serum ferritin.

    Measured: Week 9 through Week 24 and Week 37 through Week 52

  10. Mean Change in Mean Daily Dose of Iron Chelation Therapy (ICT)

    The change in daily dose for each subject is calculated as the difference of post-baseline mean daily dose and baseline mean daily dose.

    Measured: Week 9 through Week 24 and Week 37 through Week 52

  11. Proportion of subjects with progression to AML (acute myeloid leukemia)

    Time to progression to AML is defined as the time between baseline (day1 of IMP administration) and first diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.

    Measured: Week 1 to Week 52

  12. Overall survival

    Overall survival (OS) is defined as the time between start of IMP and death.

    Measured: Week 1 to Week 52

  13. Change in PRO

    In order to evaluate the Change in PRO questionnaires (from Week 1 to Week 52 and to EOT) utilizing EORTC QLQ-C30, changes from baseline in overall score and sub-scores will be calculated.

    Measured: Week 1 to Week 52 and to EOT

  14. Change in PerfO

    In order to evaluate the Change in PerfO questionnaires (from Week 1 to Week 52 and to EOT) utilizing "Timed Up and Gotest" (TUG), changes from baseline in overall score and sub-scores will be calculated.

    Measured: Week 1 to Week 52 and to EOT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2022
  2. Study start27 Oct 2021
  3. Primary completion31 Oct 2026 (estimated)
  4. Study completion28 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
International, multicenter, non-comparative, open-label, single arm study
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05181592
Sponsor's protocol ID
LUSPLUS
Acronym
LUSPLUS
Status last verified
Sep 2025
First submitted
2 Dec 2021
Last updated
30 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Luspatercept in people with Myelodysplastic Syndromes, run by GWT-TUD GmbH at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, Switzerland, Austria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

RBC-TI rate according to IWG 2018 modified criteria (time frame: from Week 1 through Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05181592.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2025.

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