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Trial record 10 of 12 for:    QUALMS

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

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ClinicalTrials.gov Identifier: NCT05384691
Recruitment Status : Not yet recruiting
First Posted : May 20, 2022
Last Update Posted : July 14, 2022
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Anne Sophie Kubasch, University of Leipzig

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : August 1, 2022
Estimated Primary Completion Date : July 31, 2026
Estimated Study Completion Date : July 31, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: LUS




Primary Outcome Measures :
  1. Erythroid response (HI-E) [ Time Frame: 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 :
  1. 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.] ]
    To evaluate HI-E response from the first day of response until loss of response.

  2. 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) ]
    To evaluate the time between start of treatment and first day of response.

  3. Neutrophil (HI-N) responses [ Time Frame: At the end of cycle 8 (each cycle is 21 days) ]
    Neutrophil (HI-N) responses according to IWG 2018 criteria

  4. Platelet (HI-P) responses [ Time Frame: At the end of cycle 8 (each cycle is 21 days) ]
    Platelet (HI-P) responses according to IWG 2018 criteria

  5. 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 ]
    Assessments will include characterization of toxicities; characterization of AEs including type, incidence, severity, seriousness, and relationship to treatment

  6. mpact 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. ]

    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.


  7. mpact of canakinumab 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 ]

    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




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05384691


Contacts
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Contact: Anne Sophie Kubasch, Dr. +49 341 97-13050 annesophie.kubasch@medizin.uni-leipzig.de
Contact: Uwe Platzbecker, Prof. Dr. uwe.platzbecker@medizin.uni-leipzig.de

Locations
Show Show 19 study locations
Sponsors and Collaborators
University of Leipzig
Celgene Corporation
Investigators
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Principal Investigator: Anne Sophie Kubasch, Dr. University Leipzig
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Responsible Party: Anne Sophie Kubasch, Coordinating Investigator, University of Leipzig
ClinicalTrials.gov Identifier: NCT05384691    
Other Study ID Numbers: LENNON Trial
First Posted: May 20, 2022    Key Record Dates
Last Update Posted: July 14, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anne Sophie Kubasch, University of Leipzig:
MDS
Anemia
Ring sideroblast
Low risk
non-transfusion dependence (NTD)
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Hematologic Diseases
Bone Marrow Diseases
Luspatercept
Hematinics