Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions

• Status: Not yet recruiting
• Trial end date: 2027-07-31
• Target enrollment: 0
• Participant gender: All

Summary

Anemia in patients with very low, low or intermediate risk myelodysplastic syndromes (MDS), that are non-transfusion dependent

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leipzig
• Collaborator: Celgene Corporation
• Treatments: Luspatercept

Criteria

Inclusion Criteria:

I01: Diagnosis of myelodysplastic syndrome (MDS) according to WHO classification I02: Very low-, low-, or intermediate-risk disease MDS with up to 3.5 according to revised International Prognostic Scoring System (IPSS-R) I03: Less than 5% blasts in bone marrow I04: Peripheral blood white blood cell (WBC) count < 13,000/μL I05: sEPO levels ≤ 500 mU/mL I06: Non-transfusion dependence (NTD) according to IWG 2018 criteria (0 - 2 RBCs during last 16 weeks) I07: Symptomatic anemia: has to be documented in the 16 weeks baseline period ending on the day of inclusion. Patients should be registered only if it is expected at time of registration that

1. a valid and complete Hb and transfusion history will be available at inclusion AND

2. the Hb Mean over the baseline period will be less than 10 g/dL I08: Age > 18 years I09: Written informed consent

Exclusion Criteria:

E01: Patient does not accept bone marrow sampling during screening and during treatment.

E02: Patient does not accept regular peripheral blood sampling for screening and during treatment.

E03: Patient does not accept subcutaneous application of LUS every three weeks E04: 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.

E05: Secondary MDS, i.e. MDS arising as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases E06: Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding.

E07: Prior allogeneic or autologous stem cell transplant E08: Prior history of AML E09:

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.

E10: Major surgery within 8 weeks prior to registration. Subjects must have completely recovered from any previous surgery prior to inclusion.

E11: Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure ≥160 mmHg or of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment E12: Platelet count < 30,000/μL (30 × 10^9/L) E13: Estimated glomerular filtration rate or creatinine clearance < 40 mL/min E14: Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) ≥ 3.0 × upper limit of normal (ULN) E15: Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≥ 3.0 × ULN E16: Total bilirubin ≥ 2.0 × ULN E17: Eastern Cooperative Oncology Group (ECOG) performance status > 2 E18: Stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to registration E19: Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months prior to registration.

E20: 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 E21: 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.

E22: History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the IMP E23: 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.

E24: Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she participates in the study E25: Subject has any condition or concomitant medication that confounds the ability to interpret data from the study.

E26: 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) E27: Pregnant or breastfeeding females E28: Positive pregnancy test in women of childbearing potential. E29: 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.

E30: 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.

E31: Participation in other interventional trials. E32: Patients under legal supervision or guardianship.