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

NCT05384691 | Recruiting Phase 2

• 1 other identifier: LENNON Trial
• Study Type: interventional
• Target: 213
• Locations: 1 country
• Sites: 22

Brief Summary

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

Conditions

Myelodysplastic Syndromes; Anemia

Keywords

MDS; Anemia; Ring sideroblast; Low risk; non-transfusion dependence (NTD)

Outcome Measures

Primary Outcomes (1)

• Erythroid response (HI-E)

  To evaluate the proportion of patients who have an erythroid response (HI-E) according to the modified IWG 2018 criteria separately for four different clinical situations (cohorts) distinguished by two factors: Serum erythropoietin (sEPO) level AND Ring sideroblast (RS) status

  At the end of cycle 8 (each cycle is 21 days)

Secondary Outcomes (7)

• HI-E response (erythroid response) duration

  From the date of treatment start until date of documented loss of response, assessed up to 18 months.]

• Time to HI-E (erythroid response)

  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

  At the end of cycle 8 (each cycle is 21 days)

• Platelet (HI-P) responses

  At the end of cycle 8 (each cycle is 21 days)

• Safety of luspatercept (toxicities and adverse events)

  From the date of treatment start until the end of study, assessed up to 48 months

Study Arms (1)

Luspatercept

OTHER

Single-arm design: All patients are treated with 1.75 mg Luspatercept per kg body weight subcutaneously on day 1 of each 21 day cycle for up to 24 weeks and in case of response for up to 1.5 years.

Drug: Luspatercept Injection

Interventions

Luspatercept Injection DRUG

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.

Also known as: LUS

Luspatercept

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leipzig: lead
• Celgene Corporation: collaborator

Study Sites (22)

Praxis für Hämatologie und Onkologie Berlin-Mitte

Berlin, 10117, Germany

NOT YET RECRUITING

Universitätsklinikum Bonn

Bonn, 53127, Germany

RECRUITING

Carl-Thiem-Klinikum Cottbus gGmbH

Cottbus, 03048, Germany

RECRUITING

OncoSearch Institut für klinische Studien GbR

Erlangen, 91052, Germany

NOT YET RECRUITING

Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie

Greifswald, 17475, Germany

NOT YET RECRUITING

OncoResearch Lerchenfeld GmbH

Hamburg, 22081, Germany

NOT YET RECRUITING

Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie

Kassel, 34125, Germany

ACTIVE NOT RECRUITING

InVO Institut für Versorgungsforschung in der Onkologie GbR

Koblenz, 56068, Germany

NOT YET RECRUITING

VK&K Studien GbR

Landshut, 84036, Germany

RECRUITING

Universität Leipzig - Medizinische Fakultät Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie

Leipzig, 04103, Germany

RECRUITING

Mannheimer Onkologie Praxis

Mannheim, 68161, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Mannheim, III Medizinische Klinik - Hämatologie und Internistische Onkologie

Mannheim, Germany

NOT YET RECRUITING

Klinikum Hochsauerland GmbH

Meschede, 59870, Germany

ACTIVE NOT RECRUITING

Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie und Gastroenterologie

Mönchengladbach, 41063, Germany

ACTIVE NOT RECRUITING

Gemeinschaftspraxis Häamto-Onkologie

München, 81241, Germany

RECRUITING

Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie

München, 81675, Germany

RECRUITING

Universitätsklinikum Münster, Medizinische Klinik A

Münster, Germany

NOT YET RECRUITING

Studiengesellschaft Onkologie Rhein/RuhrPraxis für Hämatologie und Onkologie Oberhausen und Düsseldorf

Oberhausen, 46145, Germany

ACTIVE NOT RECRUITING

Universitätsmedizin Rostock Klinik III (Hämatologie, Onkologie, Palliativmedizin) Zentrum für Innere Medizin

Rostock, 18057, Germany

NOT YET RECRUITING

Praxis ONKOSAAR Praxis für Hämatologie und Onkologie

Saarbrücken, 66113, Germany

ACTIVE NOT RECRUITING

Klinikum Mutterhaus

Trier, 54290, Germany

ACTIVE NOT RECRUITING

Universitätsklinikum Tübingen Medizinische Klinik II, AML/ALL/MDS

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Anne Sophie Kubasch, Dr.

  University Leipzig

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Sophie Kubasch, Dr.

CONTACT

+49 341 97-13050; annesophie.kubasch@medizin.uni-leipzig.de

Uwe Platzbecker, Prof. Dr.

CONTACT

uwe.platzbecker@medizin.uni-leipzig.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 20, 2022
• Study Start: September 27, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (22)