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

Sponsor

University of Leipzig (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05384691

Collaborator

Celgene Corporation (Industry)

213

Enrollment

Locations

Arm

Anticipated Duration (Months)

11.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Anemia	Drug: Luspatercept Injection	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

213 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jul 31, 2026

Anticipated Study Completion Date :

Jul 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.	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. Other Names: LUS

Arm

Intervention/Treatment

Other: 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.

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.

Other Names:

LUS

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

HI-E response (erythroid response) duration [From the date of treatment start until date of documented loss of response, assessed up to 18 months.]]
To evaluate HI-E response from the first day of response until loss of response.
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)]
To evaluate the time between start of treatment and first day of response.
Neutrophil (HI-N) responses [At the end of cycle 8 (each cycle is 21 days)]
Neutrophil (HI-N) responses according to IWG 2018 criteria
Platelet (HI-P) responses [At the end of cycle 8 (each cycle is 21 days)]
Platelet (HI-P) responses according to IWG 2018 criteria
Safety of luspatercept (toxicities and adverse events) [From the date of treatment start until the end of study, assessed up to 48 months]
Assessments will include characterization of toxicities; characterization of AEs including type, incidence, severity, seriousness, and relationship to treatment
mpact of treatment assessed by using the validated European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) [From the date of treatment start until the end of study, assessed up to 48 months.]
To assess patient-reported quality of life during CA-4948 treatment: 30 questions assessing the quality of life of oncology patients across 10 subscales will be analyzed. All subscales have a score range from 0 to 100 points. Function subscales: a higher score represents a higher quality of life. Symptoms subscales: higher score represents higher level of symptoms/problems, i.e., represents lower quality of life.
mpact of canakinumab on quality of life by using the validated Quality of Life in Myelodysplasia Scale (QUALMS) [From the date of treatment start until the end of study, assessed up to 48 months]
QoL assessment using the QUALMS questionnaire up to end of treatment: 38-item assessment tool for patients with Myelodysplastic Syndromes (MDS) QUALMS scores ranged from 24 to 99, with higher scores for better outcome

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Praxis für Hämatologie und Onkologie Berlin-Mitte	Berlin	Germany	10117
2	Carl-Thiem-Klinikum Cottbus gGmbH	Cottbus	Germany	03048
3	OncoSearch Institut für klinische Studien GbR	Erlangen	Germany	91052
4	Universitätsmedizin Greifswald Klinik Innere Medizin C / Hämatologie und Onkologie	Greifswald	Germany	17475
5	OncoResearch Lerchenfeld GmbH	Hamburg	Germany	22081
6	Klinikum Kassel GmbH Klinik für Hämatologie, Onkologie und Immunologie	Kassel	Germany	34125
7	InVO Institut für Versorgungsforschung in der Onkologie GbR	Koblenz	Germany	56068
8	VK&K Studien GbR	Landshut	Germany	84036
9	Universität Leipzig - Medizinische Fakultät Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie	Leipzig	Germany	04103
10	Mannheimer Onkologie Praxis	Mannheim	Germany	68161
11	Klinikum Hochsauerland GmbH	Meschede	Germany	59870
12	Kliniken Maria Hilf GmbH Klinik für Hämatologie, Onkologie und Gastroenterologie	Mönchengladbach	Germany	41063
13	Gemeinschaftspraxis Häamto-Onkologie	München	Germany	81241
14	Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie	München	Germany	81675
15	Studiengesellschaft Onkologie Rhein/RuhrPraxis für Hämatologie und Onkologie Oberhausen und Düsseldorf	Oberhausen	Germany	46145
16	Universitätsmedizin Rostock Klinik III (Hämatologie, Onkologie, Palliativmedizin) Zentrum für Innere Medizin	Rostock	Germany	18057
17	Praxis ONKOSAAR Praxis für Hämatologie und Onkologie	Saarbrücken	Germany	66113
18	Klinikum Mutterhaus	Trier	Germany	54290
19	Universitätsklinikum Tübingen Medizinische Klinik II, AML/ALL/MDS	Tübingen	Germany	72076