The purpose of the study is to determine wheter patients with chronic lymphocytic leukaemia (CLL) will benefit from vaccination with conjugated pneumococcal vaccine compared to conventional 23-valent capsular polysaccarid vaccine in terms of immune response and infections.
Conditions
Interventions
Trade Name: Pneumovax
Product Name: Pneumovax
Pharmaceutical Form: Solution for solution for injection
Trade Name: Prevenar
Product Name: Prevenar
Pharmaceutical Form: Solution for injection
Sponsors
Swedish CLL-group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Untreated CLL patients all Rai stages (0 to IV), as early as possible after diagnosis, always before any therapy with monoclonal antibodies and /or chemotherapy. Extension study: CLL patients earlier included in the Pneumococcal vaccination study, who have received either PPSV23 or PCV13 and who have not received any additional pneumococcal vaccine outside the study protocol after 2013-2016 are eligible for analysis of the long-term immune response. The same patients are eligible for revaccination if they do not meet any exclusion criteria. Ongoing or recent CLL specific treatment is not an exclusion criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: Patients for whom immunosuppressive therapy is planned to start within one month. • Patients with other malignancies • Patients receiving corticosteroids or other immunosuppressive drugs • Patients who have had an allergic reaction to any vaccination in the past • Patients with neutropenia (PMNs < 500 cells/mm3) • Patients with a positive DAT (Direct Antiglobulin Test) or known previous hemolysis • Patients failing to give informed consent. • Patients with ongoing immunoglobulin therapy • Patients with known HIV infection • Patients who have previously received pneumococcal vaccine within 5 years • Active infection Extension study: • Patients receiving high dose corticosteroids or other immunosuppressive drugs that is not part of active CLL treatment • Patients who have had an allergic reaction to any vaccination in the past • Patients with a positive DAT (Direct Antiglobulin Test) or known present or previous hemolysis, ITP and Guillain-Barre • Patients failing to give informed consent • Patients with ongoing immunoglobulin therapy • Patients with known HIV infection • Patients who have received a pneumococcal vaccine after the study vaccine was given. • Active infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the immune response to the 13 common serotypes in 13-valent conjugated (vPnC) vaccine compared to the response to vaccination with the 23-valent polysaccharide (23vPS) vaccine, measured as the percentage of subjects with a positive vaccination response in the two groups. A positive vaccination response is defined as an OPA titer (= LLOQ) in 8 out of the 13 measured serotypes collected 1 month after vaccination. Extension study: - To determine the long term immunological response after vaccination with either PPSV23 or PCV13 in the cohort from our previous randomized phase III trial. - To study the effect of revaccination with PCV13 in both vaccination groups and to investigate if there is an additive effect of another dose of PCV13 in patients with CLL. For the group that did not receive PPSV23 in the randomized trial, this vaccine will be given to broaden the serotype response and determine the additive effect after PCV13 vaccination. ;Secondary Objective: To study the immune response to the 13 common serotypes in the 13vPnC- and the 23vPS-vaccine, measured by ELISA as serotype-specific IgG antibody levels collected 1 month and 6 months after vaccination. -To study the immune response to the 13 common serotypes in 13vPnC and 23vPS, measured as OPA (GMTs) 6 months after vaccination. -The serotype-specific IgG antibody levels, as measured by ELISA, geometric mean concentrations (GMCs) will be compared between the two vaccine groups. Extension study: Nasopharyngeal samples will be collected at inclusion and after 6 and 12 months to determine throat colonization of the study groups. The national registry of the public health agency will be used to verify if a subject has experienced an invasive pneumococcal infection with a serotype included in the administrated vaccine. Additional blood samples will be collected and stored for later investigation of biomarkers involved in the immune response to pneumococcal vaccination.;Primar | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To study the immune response to the 13 common serotypes in the 13vPnC- and the 23vPS-vaccine, measured by ELISA as serotype-specific IgG antibody levels collected 1 month and 6 months after vaccination. -To study the immune response to the 13 common serotypes in 13vPnC and 23vPS, measured as OPA (GMTs) 6 months after vaccination. -The serotype-specific IgG antibody levels, as measured by ELISA, geometric mean concentrations (GMCs) will be compared between the two vaccine groups. Extension study: - To compare ELISA GMCs for each serotype measured 3-5 years after vaccination - To compare immune response in terms of OPA titers 12 months after revaccination, using the same means of comparison as for the primary end point. - To compare ELISA GMCs for each serotype measured two, six and twelve months after revaccination. - To detect the incidence of pneumococcal colonization through culture of nasopharyngeal swabs at inclusion, after six and twelve months. - To trace if any of the vaccinated patients had any episode of invasive pneumococcal disease (and if so, to define the serotype) through registries from The Public Health Agency of Sweden. - To explore factors that possibly influence immune responses to vaccination, like disease progression, earlier or ongoing CLL specific treatment. - To collect and store blood samples for further investigation of biomarkers that are involved in the immune response to pneumococcal vaccination strategies. ;Timepoint(s) of evaluation of this end point: 1 month and 6 months after vaccination Extension study: 3-5 years after initial vaccination Evaluation at 8 weeks, 6 and 12 months after revaccination. | — |
Countries
Sweden
Contacts
Public ContactDept of Medicine, Hematology
Region Örebro län
Outcome results
None listed