Anemia, Myelodysplastic Syndromes
Conditions
Keywords
anemia, low risk MDS, inflammation, IL-1beta blockade, NLRP3 activation
Brief summary
Hematologic improvement of erythrocytes after 6 months of canakinumab treatment.
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.
Interventions
Administration for a duration of 6 months for all patients and in case of response further treatment for up to three years
Sponsors
Novartis Pharmaceuticals
University of Leipzig
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of 1. Lower-risk myelodysplastic syndrome (MDS) 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. Symptomatic anemia (all NTD, LTB, or HTB): has to be documented in the 16 weeksbaseline 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 OR three or more RBC-transfusions will have been given during the baseline period documenting transfusion dependence. 4. Documented transfusion strategy: A transfusion trigger threshold is needed which characterizes the transfusion strategy - ideally for the whole baseline period, but at least for the time from registration to the end of the study. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HI-E after 6 months of treatment | 6 months | Erythroid response rate (HI-E) of canakinumab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Disease progression | after 24 weeks | Proportion of disease progression (after reaching PD at any time during the trial after primary end-point visit) |
| 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 outcome |
| 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) | 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 |
Countries
Germany
Outcome results
None listed