Luspatercept for treating anemia in low-risk myelodysplastic syndromes

A Phase II, Open-label, Single Arm Study to Evaluate the Efficacy of Luspatercept in Erythropoiesis-stimulating Agent Naive Lower-risk MDS Patients With or Without Ring Sideroblasts Who do Not Require RBC Transfusions

This study is testing if Luspatercept can help people with low-risk myelodysplastic syndromes who have anemia feel better without needing blood transfusions.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 213 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Leipzig (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 22 sites (Berlin and 21 other locations)
• Trial ID: NCT05384691 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of Luspatercept in patients with very low, low, or intermediate-risk myelodysplastic syndromes (MDS) who are experiencing anemia and are not dependent on transfusions. The study focuses on ESA-naive patients, meaning they have not previously received erythropoiesis-stimulating agents. Participants will receive Luspatercept injections every three weeks, and their response to treatment will be monitored through regular blood sampling and bone marrow assessments. The goal is to determine if Luspatercept can effectively improve anemia symptoms in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with very low, low, or intermediate-risk MDS who are experiencing symptomatic anemia and are not dependent on transfusions.

Not a fit: Patients who have previously received treatment for anemia associated with MDS or those unwilling to undergo necessary blood sampling may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with anemia due to low-risk MDS.

How similar studies have performed: While there have been studies on treatments for MDS, the specific use of Luspatercept in this non-transfusion dependent population is a novel approach.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of myelodysplastic syndrome (MDS) according to WHO classification
* Very low-, low-, or intermediate-risk disease MDS with up to 3.5 according to revised International Prognostic Scoring System (IPSS-R)
* Less than 5% blasts in bone marrow
* Peripheral blood white blood cell (WBC) count \< 13,000/μL
* sEPO levels ≤ 500 mU/mL
* Non-transfusion dependence (NTD) according to IWG 2018 criteria
* Symptomatic anemia
* Age \> 18 years
* Written informed consent

Exclusion Criteria:

* Patient does not accept bone marrow sampling during screening and during treatment
* Patient does not accept regular peripheral blood sampling for screening and during treatment.
* Patient does not accept subcutaneous application of LUS every three weeks
* Prior treatment for anemia associated with MDS (i.e. ESA, luspatercept), except previously treated with G-CSF/granulocyte-macrophage colony-stimulating factor (GM-CSF), both agents must be discontinued at least 4 weeks before registration
* Secondary MDS, i.e. MDS arising 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.
* Prior allogeneic or autologous stem cell transplant
* Prior history of AML
* 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.
* Major surgery within 8 weeks prior to registration.
* Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure ≥160 mmHg or of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment
* Platelet count \< 30,000/μL (30 × 10\^9/L)
* Estimated glomerular filtration rate or creatinine clearance \< 40 mL/min
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) ≥ 3.0 × upper limit of normal (ULN)
* Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≥ 3.0 × ULN
* Total bilirubin ≥ 2.0 × ULN
* Eastern Cooperative Oncology Group (ECOG) performance status \> 2
* Stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to registration
* Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months prior to registration.
* Subjects with a known ejection fraction of ˂ 35%, confirmed by a local echocardiography or multigated acquisition scan (MUGA) performed within 6 months prior to registration, 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 has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (e.g., imprisoned or institutionalized) that would prevent the subject from participating in the study.
* Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she participates in the study
* Subject has any condition or concomitant medication that confounds the ability to interpret data from the study.
* Use of any of the following within five weeks prior to registration are prohibited: Anticancer cytotoxic chemotherapeutic agent or treatment, Corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to inclusion for medical conditions other than MDS, Iron chelation therapy, except for subjects on a stable or decreasing dose for at least 8 weeks prior to registration, Other RBC hematopoietic growth factors (e.g. interleukin \[IL\]-3)
* Pregnant or breastfeeding females
* Positive pregnancy test in women of childbearing potential.
* Female subjects of childbearing potential unwilling to use a highly effective method of contraception for the course of the study through 90 days after the last dose of study medication.
* Male subjects with procreative capacity not willing to use a highly effective method of contraception, starting with the first dose of study therapy through 90 days after the last dose of study therapy.
* Participation in other interventional trials.
* Patients under legal supervision or guardianship.

Where this trial is running

Berlin and 21 other locations

• Praxis für Hämatologie und Onkologie Berlin-Mitte — Berlin, Germany (NOT_YET_RECRUITING)
• Universitätsklinikum Bonn — Bonn, Germany (RECRUITING)
• Carl-Thiem-Klinikum Cottbus gGmbH — Cottbus, Germany (RECRUITING)
• OncoSearch Institut für klinische Studien GbR — Erlangen, Germany (NOT_YET_RECRUITING)
• Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie — Greifswald, Germany (NOT_YET_RECRUITING)
• OncoResearch Lerchenfeld GmbH — Hamburg, Germany (NOT_YET_RECRUITING)
• Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie — Kassel, Germany (ACTIVE_NOT_RECRUITING)
• InVO Institut für Versorgungsforschung in der Onkologie GbR — Koblenz, Germany (NOT_YET_RECRUITING)
• VK&K Studien GbR — Landshut, Germany (RECRUITING)
• Universität Leipzig - Medizinische Fakultät Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie — Leipzig, Germany (RECRUITING)
• Mannheimer Onkologie Praxis — Mannheim, Germany (ACTIVE_NOT_RECRUITING)
• Universitätsklinikum Mannheim, III Medizinische Klinik - Hämatologie und Internistische Onkologie — Mannheim, Germany (NOT_YET_RECRUITING)
• Klinikum Hochsauerland GmbH — Meschede, Germany (ACTIVE_NOT_RECRUITING)
• Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie und Gastroenterologie — Mönchengladbach, Germany (ACTIVE_NOT_RECRUITING)
• Gemeinschaftspraxis Häamto-Onkologie — München, Germany (RECRUITING)
• Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie — München, Germany (RECRUITING)
• Universitätsklinikum Münster, Medizinische Klinik A — Münster, Germany (NOT_YET_RECRUITING)
• Studiengesellschaft Onkologie Rhein/RuhrPraxis für Hämatologie und Onkologie Oberhausen und Düsseldorf — Oberhausen, Germany (ACTIVE_NOT_RECRUITING)
• Universitätsmedizin Rostock Klinik III (Hämatologie, Onkologie, Palliativmedizin) Zentrum für Innere Medizin — Rostock, Germany (NOT_YET_RECRUITING)
• Praxis ONKOSAAR Praxis für Hämatologie und Onkologie — Saarbrücken, Germany (ACTIVE_NOT_RECRUITING)
• Klinikum Mutterhaus — Trier, Germany (ACTIVE_NOT_RECRUITING)
• Universitätsklinikum Tübingen Medizinische Klinik II, AML/ALL/MDS — Tübingen, Germany (RECRUITING)

Study contacts

• Principal investigator: Anne Sophie Kubasch, Dr. — University Leipzig
• Study coordinator: Anne Sophie Kubasch, Dr.

Conditions: Myelodysplastic Syndromes, Anemia, MDS, Ring sideroblast, Low risk, non-transfusion dependence