Clinical trial NCT05384691: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Anemia
Keywords: MDS
Anemia
Ring sideroblast
Low risk
non-transfusion dependence (NTD)
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2022-05-20
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Primary outcomes:
measure: Erythroid response (HI-E)
timeFrame: At the end of cycle 8 (each cycle is 21 days)
Secondary outcomes:
measure: HI-E response (erythroid response) duration
timeFrame: From the date of treatment start until date of documented loss of response, assessed up to 18 months.]
measure: Time to HI-E (erythroid response)
timeFrame: From the date of treatment start until first day of response, assessed up to end of cycle 8 (each cycle is 21 days)
measure: Neutrophil (HI-N) responses
timeFrame: At the end of cycle 8 (each cycle is 21 days)
measure: Platelet (HI-P) responses
timeFrame: At the end of cycle 8 (each cycle is 21 days)
measure: Safety of luspatercept (toxicities and adverse events)
timeFrame: From the date of treatment start until the end of study, assessed up to 48 months
measure: Impact of treatment assessed by using the validated European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30)
timeFrame: From the date of treatment start until the end of study, assessed up to 48 months.
measure: Impact of luspatercept on quality of life by using the validated Quality of Life in Myelodysplasia Scale (QUALMS)
timeFrame: From the date of treatment start until the end of study, assessed up to 48 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Praxis für Hämatologie und Onkologie Berlin-Mitte
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus gGmbH
city: Erlangen
country: Germany
facility: OncoSearch Institut für klinische Studien GbR
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie
city: Koblenz
country: Germany
facility: InVO Institut für Versorgungsforschung in der Onkologie GbR
city: Landshut
country: Germany
facility: VK&K Studien GbR
city: Leipzig
country: Germany
facility: Universität Leipzig - Medizinische Fakultät Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie
city: Mannheim
country: Germany
facility: Mannheimer Onkologie Praxis
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, III Medizinische Klinik - Hämatologie und Internistische Onkologie
city: Meschede
country: Germany
facility: Klinikum Hochsauerland GmbH
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie und Gastroenterologie
city: München
country: Germany
facility: Gemeinschaftspraxis Häamto-Onkologie
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik A
city: Oberhausen
country: Germany
facility: Studiengesellschaft Onkologie Rhein/RuhrPraxis für Hämatologie und Onkologie Oberhausen und Düsseldorf
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock Klinik III (Hämatologie, Onkologie, Palliativmedizin) Zentrum für Innere Medizin
city: Saarbrücken
country: Germany
facility: Praxis ONKOSAAR Praxis für Hämatologie und Onkologie
city: Trier
country: Germany
facility: Klinikum Mutterhaus
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen Medizinische Klinik II, AML/ALL/MDS
Study officials:
affiliation: University Leipzig
name: Anne Sophie Kubasch, Dr.
role: PRINCIPAL_INVESTIGATOR
References: