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

Official title

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

Overview

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

Detailed description

Patients with very low, low or intermediate risk myelodysplastic syndromes (MDS) presenting with anemia, transfusion independence (NTD) and naive towards ESA treatment

Interventions

• Drug Luspatercept Injection
  All formally included patients will receive 1.75 mg/kg luspatercept administered subcutaneously every three weeks (on day 1 of each 21-day cycle) for a duration of 24 weeks. Responders at the response assessment (according to HI-E) in week 25 will be further treated with 1.75 mg/kg luspatercept until loss of response for an expected maximum of 18 months.

Primary outcome measures

• Erythroid response (HI-E) [Time frame: At the end of cycle 8 (each cycle is 21 days)]

Secondary outcome measures (7)

• HI-E response (erythroid response) duration [Time frame: From the date of treatment start until date of documented loss of response, assessed up to 18 months.]]
• Time to HI-E (erythroid response) [Time frame: From the date of treatment start until first day of response, assessed up to end of cycle 8 (each cycle is 21 days)]
• Neutrophil (HI-N) responses [Time frame: At the end of cycle 8 (each cycle is 21 days)]
• Platelet (HI-P) responses [Time frame: At the end of cycle 8 (each cycle is 21 days)]
• Safety of luspatercept (toxicities and adverse events) [Time frame: From the date of treatment start until the end of study, assessed up to 48 months]
• Impact of treatment assessed by using the validated European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) [Time frame: From the date of treatment start until the end of study, assessed up to 48 months.]
• Impact of luspatercept on quality of life by using the validated Quality of Life in Myelodysplasia Scale (QUALMS) [Time frame: From the date of treatment start until the end of study, assessed up to 48 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 22 centers

• Praxis für Hämatologie und Onkologie Berlin-Mitte — Berlin
• Universitätsklinikum Bonn — Bonn
• Carl-Thiem-Klinikum Cottbus gGmbH — Cottbus
• OncoSearch Institut für klinische Studien GbR — Erlangen
• Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie — Greifswald
• OncoResearch Lerchenfeld GmbH — Hamburg
• Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie — Kassel
• InVO Institut für Versorgungsforschung in der Onkologie GbR — Koblenz
• … and 14 more centers

Identifiers

NCT: NCT05384691 · LENNON Trial

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗