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Trial record 8 of 12 for:    QUALMS

Efficacy and Safety of Canakinumab for the Treatment of Anemia in LR-MDS Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05237713
Recruitment Status : Recruiting
First Posted : February 14, 2022
Last Update Posted : July 12, 2022
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Anne Sophie Kubasch, University of Leipzig

Brief Summary:
Hematologic improvement of erythrocytes after 6 months of canakinumab treatment.

Condition or disease Intervention/treatment Phase
Anemia Myelodysplastic Syndromes Drug: Canakinumab Injection Phase 2

Detailed Description:
To study the erythroid response rate (HI-E) of canakinumab in patients with IPSS-R very low, low, or intermediate risk MDS or MDS/MPN after 6 months of treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single-Arm, Open-Label Study to Assess the Efficacy and Safety of Canakinumab for the Treatment of Anemia in Patients With IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes or MDS/MPN
Actual Study Start Date : April 26, 2022
Estimated Primary Completion Date : February 29, 2028
Estimated Study Completion Date : February 29, 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Canakinumab

Arm Intervention/treatment
Canakinumab treatment
200 mg canakinumab subcutaneously every three weeks
Drug: Canakinumab Injection
Administration for a duration of 6 months for all patients and in case of response further treatment for up to three years
Other Name: Ilaris(R)




Primary Outcome Measures :
  1. HI-E after 6 months of treatment [ Time Frame: 6 months ]
    Erythroid response rate (HI-E) of canakinumab


Secondary Outcome Measures :
  1. HI-E response duration [ Time Frame: up to three years ]
    Duration of erythroid response rate will be measured up to loss of response or reaching end of study (after max. 3 years of treatment)

  2. Number of (serious) adverse events [ Time Frame: up to three years ]
    The safety profile of canakinumab will be described by collecting AE (adverse event) and SAE (serious adverse event) information up to the start of new treatment or reaching end of study (after max. 3 years of treatment). Special consideration will be laid on events that lead to treatment discontinuation.

  3. Disease progression [ Time Frame: after 24 weeks ]
    Proportion of disease progression (after reaching PD at any time during the trial after primary end-point visit)

  4. Impact 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 36 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


  5. Impact of canakinumab on quality of life 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 36 months ]

    QoL assessment using the EORTC-C30 questionnaire up to end of treatment:

    To assess patient-reported quality of life during canakinumab 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




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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:

  1. Diagnosis of

    1. Lower-risk myelodysplastic syndrome (MDS)17 OR
    2. Myelodysplastic/myeloproliferative neoplasm (MDS/MPN) including MDS/MPN-RS-T, MDS/MPNu, aCML, or CMML (as per the World Health Organization [WHO] 2016 classification) Note: Diagnoses will be confirmed by central morphological review during screening assessment
  2. Very low, low or intermediate risk disease MDS with up to 3.5 points according to the revised International Prognostic Scoring System (IPSS-R) classification (to be confirmed during screening assessment). For MDS/MPN < 10% bone marrow blasts at screening. For CMML low or intermediate risk according to CMML-Specific Prognostic Scoring System (CPSS Score).
  3. Non-transfusion dependence (NTD) according to IWG 2018 criteria (0-2 RBCs during last 16 weeks)
  4. Symptomatic anemia: has to be documented in the 16 weeks baseline period ending on the day of inclusion. Patients should be registered only if it is expected at time of registration that

    1. a valid and complete hemoglobin and transfusion history will be available at inclusion AND
    2. the hemoglobin mean over the baseline period will be less than 10 g/dL
  5. Relapsed / refractory / intolerant / ineligible (endogenous serum erythropoietin levels ≥ 200 U/L) to ESA treatment
  6. Age ≥ 18 years
  7. Written informed consent

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the trial.

Compliance with major study procedures

  1. Patient does not accept bone marrow sampling during screening and treatment period.
  2. Patient does not accept peripheral blood sampling for screening and during treatment.
  3. Patient does not accept subcutaneous application of canakinumab every three weeks

    Contraindications

  4. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding

    a. iron deficiency must be determined by calculated transferrin saturation (iron/total iron binding capacity) ≤ 20%, or serum ferritin ≤ 15 µg/L

  5. Prior allogeneic or autologous stem cell transplant
  6. Known history of diagnosis of AML

    Safety

  7. Severe neutropenia defined by ANC ≤ 0.5 Gpt/l
  8. Severe thrombocytopenia with platelets (PLT) < 30 Gpt/L
  9. Serum creatinine > 1.5x ULN OR measured or calculated creatinine clearance < 40 ml/min (NOTE: creatinine clearance should be calculated per institutional standard. GFR can also be used)
  10. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) - both have to be measured
  11. Eastern Cooperative Oncology Group (ECOG) > 2
  12. Total bilirubin ≥ 2.0 x ULN

    1. higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis).
    2. subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs' test or over 50% indirect bilirubin
  13. Active second malignancy at time of study entry
  14. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:

    1. Basal or squamous cell carcinoma of the skin
    2. Carcinoma in situ of the cervix
    3. Carcinoma in situ of the breast
    4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
  15. Major surgery within 8 weeks prior to screening (NOTE: Subjects must have completely recovered from any previous surgery prior to inclusion)
  16. Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months prior to screening
  17. Positive test result as an indicator for active or latent tuberculosis (evaluation performed per local treatment guidelines or clinical practice)
  18. Subjects with suspected or proven immunocompromised state or infections, including:

    1. Known history of testing positive for Human Immunodeficiency Virus (HIV) infections.
    2. Known active or recurrent, hepatitis B and C (positive or indeterminate laboratory results).
    3. Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy.
    4. Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g.: Prednisone >20 mg (or equivalent) oral or intravenous daily for >14 days; Prednisone > 5 mg and ≤ 20 mg (or equivalent) daily for > 30 days; Equivalent dose of methotrexate >15 mg weekly.
    5. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator´s Brochure).

    Excluded treatments before and during study treatment

  19. Anticancer cytotoxic chemotherapeutic agent or treatment for at least 14 days prior to registration and during study treatment
  20. Corticosteroids or other immunosuppressive therapies (TNF-Blocker, other IL-1 Blocking Agent, Disease-modifying anti-rheumatic drugs (DMARDs) including ciclosporin, cyclophosphamide, hydroxychloroquine, leflunomide, methotrexate, mycophenolate, sulfasalazine) for at least 14 days prior to registration and during study treatment
  21. Treatment with ESAs, luspatercept, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) for at least 14 days prior to registration and during study treatment
  22. Treatment with disease modifying agents (eg, immune-modulatory drugs [IMiDs such as lenalidomide, hypomethylating agents] or experimental agents for underlying MDS disease for at least 14 days prior to registration and during study treatment
  23. Prior treatment with canakinumab
  24. Live vaccination during study treatment

    Special considerations for females

  25. Pregnant or breastfeeding females
  26. Positive pregnancy test in women of childbearing potential NOTE: Urine or serum pregnancy test should be repeated within 3 days prior to receiving study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required additionally
  27. Female subjects of childbearing potential unwilling to use an adequate method of contraception for the course of the study through 90 days after the last dose of study medication NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

    Special considerations for males

  28. Male subjects with procreative capacity not willing to use an adequate method of contraception, starting with the first dose of study therapy through 90 days after the last dose of study therapy NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

    Regulatory requirements

  29. Participation in other interventional trials
  30. 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): NCT05237713


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
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Germany
Medizinisches Versorgungszentrum "Onkologischer Schwerpunkt am Oskar- Helene-Heim" Recruiting
Berlin, Germany, 14195
Contact: Philipp Kiewe, PD Dr.         
Principal Investigator: Philipp Kiewe, PD Dr.         
Sub-Investigator: Markus Schuler, PD Dr.         
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Medizinischen Klinik und Poliklinik I / Hämatologie Recruiting
Dresden, Germany, 01307
Contact: Katja Sockel, Dr.         
Principal Investigator: Katja Sockel, Dr.         
Sub-Investigator: Theresa Kretschmann, Dr.         
Universitätsklinikum Düsseldorf Klinik f. Hämatologie, Onkologie und klinische Immunologie Not yet recruiting
Düsseldorf, Germany, 40225
Contact: Ulrich Germing, Prof. Dr.         
Principal Investigator: Ulrich Germing, Prof. Dr.         
Sub-Investigator: Claudia Lesch, Dr.         
Klinik und Poliklinik für Hämatologie und Zelltherapie, Hämostaseologie Recruiting
Leipzig, Germany, 04318
Contact: Anne Sophie Kubasch         
Principal Investigator: Anne Sophie Kubasch, Dr.         
Sub-Investigator: Platzbecker Uwe, Prof. Dr.         
Rotkreuzklinikum München III. Medizinische Abteilung Recruiting
Munich, Germany, 80634
Contact: Alexander Höllein, PD Dr.         
Principal Investigator: Alexander Höllein, PD Dr.         
Sub-Investigator: Sebastian Schulz, Dr.         
Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie Recruiting
Munich, Germany, 81675
Contact: Katharina Götze, Prof. Dr.         
Principal Investigator: Katharina Götze, Prof. Dr.         
Sub-Investigator: Anna Hecht, Dr.         
Sponsors and Collaborators
University of Leipzig
Novartis Pharmaceuticals
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: NCT05237713    
Other Study ID Numbers: CANFIRE
First Posted: February 14, 2022    Key Record Dates
Last Update Posted: July 12, 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:
anemia
low risk MDS
inflammation
IL-1beta blockade
NLRP3 activation
Additional relevant MeSH terms:
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Preleukemia
Anemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms