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
- Conditions
- Lower-risk MDS or MDS/MPN
- Registration Number
- 2024-515886-33-00
- Lead Sponsor
- Universitaet Leipzig
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 11
Cytomorphology based confirmed diagnosis of lower-risk MDS or MDS/MPN including MDS/MPN-RS-T, MDS/MPNu, aCML or CMML (as per the World Health Organization [WHO] 2016 classification)
IPSS-R up to 3.5: very low/low/intermediate risk disease (MDS); MDS/MPN < 10% bone marrow blasts; CPSS-Score low/intermediate for CMML
Symptomatic anemia (based on complete Hb time course and transfusion history)
Relapsed / refractory / intolerant / ineligible (sEPO ≥ 200 U/L) to ESA treatment
Age ≥ 18 years
Written informed consent
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
Active second malignancy
Prior or concomitant treatment with anticancer medications or disease modifying agents
Previously treated with canakinumab
Prior allogeneic or autologous stem cell transplant
Known history of diagnosis of AML
Severe neutropenia (ANC 0.5 Gpt/L)
Severe thrombocytopenia (PLT <30 Gpt/L)
Serum creatinine > 1.5x ULN OR measured or calculated creatinine clearance < 40 ml/min
AST or ALT ≥ 3.0 x ULN
ECOG > 2
Total bilirubin ≥ 2.0 x ULN
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method The primary clinical endpoint “documented achievement of erythroid response (HI-E)” is based on internationally accepted and validated IWG 2018 response criteria and defined as an increase in hemoglobin levels by at least 1.5 g/dL, persistent for at least 8 weeks over the baseline hemoglobin level (mean over 16 weeks prior to inclusion) for NTD patients or no transfusions within a 8 week-window for LTB and HTB (major response), and will be determined after 8 cycles of canakinumab treatment. The primary clinical endpoint “documented achievement of erythroid response (HI-E)” is based on internationally accepted and validated IWG 2018 response criteria and defined as an increase in hemoglobin levels by at least 1.5 g/dL, persistent for at least 8 weeks over the baseline hemoglobin level (mean over 16 weeks prior to inclusion) for NTD patients or no transfusions within a 8 week-window for LTB and HTB (major response), and will be determined after 8 cycles of canakinumab treatment.
- Secondary Outcome Measures
Name Time Method Disease progression after 24 weeks Proportion of disease progression (after reaching PD at any time during the trial after primary end-point visit)
HI-E response duration 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)
Number of (serious) adverse events 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.
Impact 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 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 outcomeImpact 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) 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
Trial Locations
- Locations (2)
Onkologischer Schwerpunkt Am Oskar Helene Heim MVZ
🇩🇪Berlin, Germany
Universitaet Leipzig
🇩🇪Leipzig, Germany
Onkologischer Schwerpunkt Am Oskar Helene Heim MVZ🇩🇪Berlin, GermanyPhilipp KieweSite contact+49030644995130philipp.kiewe@onkologie-ohh.de