E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Lymphocytic Leukemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
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 compare long term immune response between the two groups 3-5 years after vaccination with PCV13 or PPSV23 - to measure immune response two months after revaccinating of both groups with PCV13 and add PPSV23 to the group not previously given a polysaccharide vaccine - to measure immune responses 6 months after the last PCV13 vaccination
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 month after vaccination
Extension study: 3-5 years after initial vaccination Evaluation at 8 weeks, 6 and 12 months after revaccination. |
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E.5.2 | 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.
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |