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

NCT05181592 | Active Not Recruiting Phase 3

• 1 other identifier: LUSPLUS
• Study Type: interventional
• Target: 70
• Locations: 4 countries
• Sites: 13

Brief 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)

Conditions

Myelodysplastic Syndromes

Keywords

MDS; Luspatercept; myelodysplastic syndrome; ring-sideroblastic phenotype; MDS-RS

Outcome Measures

Primary Outcomes (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).

  from Week 1 through Week 24

Secondary Outcomes (14)

• RBC-TI rate according to IWG 2006 criteria

  from Week 1 through Week 24 and through Week 52

• Median time to RBC-TI

  Week 1 through Week 24 and through Week 52

• Median Duration of RBC-TI

  Week 1 through Week 24 and through Week 52

• Change in RBC units transfused

  Week 9 through Week 24 and Week 37 through Week 52

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

  Week 1 through Week 24 and through Week 52

Study Arms (1)

Luspatercept (single arm)

EXPERIMENTAL

open-label, single-arm

Drug: Luspatercept

Interventions

Luspatercept DRUG

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

Also known as: Reblozyl

Luspatercept (single arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Celgene: collaborator

Study Sites (13)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Medizinische Universität Wien

Vienna, 1090, Austria

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar

München, 81675, Germany

Location

Institut Català d' Oncologia de Badalona

Badalona, 8916, Spain

Location

Hospital Vall d´Hebron

Barcelona, 08023, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28009, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

University Hospital of Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario y Politecnico La Fe de Valencia

Valencia, 46026, Spain

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Clinica di Ematologia Istituto oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Katharina Götze, Prof.

  Klinikum rechts der Isar der Technischen Universität München

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: International, multicenter, non-comparative, open-label, single arm study

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: January 6, 2022
• Study Start: October 27, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); AU (2); DE (2); CH (3)