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

NCT ID: NCT05384691

Last Updated: 2024-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

213 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-27

Study Completion Date

2027-07-31

Brief Summary

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

Detailed Description

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

Conditions

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Myelodysplastic Syndromes Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Luspatercept

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.

Group Type OTHER

Luspatercept Injection

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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LUS

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene Corporation

INDUSTRY

Sponsor Role collaborator

University of Leipzig

OTHER

Sponsor Role lead

Responsible Party

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Anne Sophie Kubasch

Coordinating Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anne Sophie Kubasch, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Leipzig

Locations

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Praxis für Hämatologie und Onkologie Berlin-Mitte

Berlin, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Bonn

Bonn, , Germany

Site Status RECRUITING

Carl-Thiem-Klinikum Cottbus gGmbH

Cottbus, , Germany

Site Status RECRUITING

OncoSearch Institut für klinische Studien GbR

Erlangen, , Germany

Site Status NOT_YET_RECRUITING

Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie

Greifswald, , Germany

Site Status NOT_YET_RECRUITING

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie

Kassel, , Germany

Site Status ACTIVE_NOT_RECRUITING

InVO Institut für Versorgungsforschung in der Onkologie GbR

Koblenz, , Germany

Site Status NOT_YET_RECRUITING

VK&K Studien GbR

Landshut, , Germany

Site Status RECRUITING

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

Leipzig, , Germany

Site Status RECRUITING

Mannheimer Onkologie Praxis

Mannheim, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Mannheim, III Medizinische Klinik - Hämatologie und Internistische Onkologie

Mannheim, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Hochsauerland GmbH

Meschede, , Germany

Site Status ACTIVE_NOT_RECRUITING

Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie und Gastroenterologie

Mönchengladbach, , Germany

Site Status ACTIVE_NOT_RECRUITING

Gemeinschaftspraxis Häamto-Onkologie

München, , Germany

Site Status RECRUITING

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

München, , Germany

Site Status RECRUITING

Universitätsklinikum Münster, Medizinische Klinik A

Münster, , Germany

Site Status NOT_YET_RECRUITING

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

Oberhausen, , Germany

Site Status ACTIVE_NOT_RECRUITING

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

Rostock, , Germany

Site Status NOT_YET_RECRUITING

Praxis ONKOSAAR Praxis für Hämatologie und Onkologie

Saarbrücken, , Germany

Site Status ACTIVE_NOT_RECRUITING

Klinikum Mutterhaus

Trier, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Tübingen Medizinische Klinik II, AML/ALL/MDS

Tübingen, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Anne Sophie Kubasch, Dr.

Role: CONTACT

+49 341 97-13050

Uwe Platzbecker, Prof. Dr.

Role: CONTACT

Facility Contacts

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Stephan Fuhrmann, Dr.

Role: primary

Karin Mayer, Dr.

Role: primary

Maximilian Desole, Dr.

Role: primary

Babette Häcker, Dr.

Role: primary

Florian Heidel, Prof. Dr.

Role: primary

Thomas Wolff, Dr.

Role: primary

Christoph Lutz, PD Dr.

Role: primary

Florian Kaiser, PD Dr.

Role: primary

Anne Sophie Kubasch, Dr.

Role: primary

Daniel Nowak, Prof.

Role: primary

Matthias Zingerle, Dr.

Role: primary

Katharina Götze, Prof. Dr.

Role: primary

Jan-Henrik Mikesch, PD Dr.

Role: primary

Christoph Wittke, Dr.

Role: primary

Maximilian Christopeit, PD Dr.

Role: primary

Other Identifiers

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LENNON Trial

Identifier Type: -

Identifier Source: org_study_id

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