The aim of the study is to evaluate pneumococcal vaccination strategy with PPSV23 and PCV13 in patients with chronic lymphocytic leukemia (CLL) initially randomized in a clinical study.
Conditions
Interventions
Trade Name: Pneumovax
Product Name: Pneumovax
Pharmaceutical Form: Solution for injection in pre-filled syringe
Trade Name: Prevenar
Product Name: Prevenar
Pharmaceutical Form: Suspension for injecti
Sponsors
Swedish CLL-group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: CLL patients CLL patients earlier included in the Pneumococcal vaccination study 0887x1-20003 (EudraCT No: 2009-012642-22), who have received either PCV13 or PPSV23 are eligible for evaluation of the long-term immune response. The median age of the patient group was at inclusion 70 years (range 46-87) with an equal number men and women (65/63). 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. Controls A control group (n=40) of immunocompetent subjects will be recruited in Region Örebro County. The control group will be matched to the CLL group by age and gender. For inclusion they should have been vaccinated with either PCV13 (n=20) or PPSV23 (n=20) approximately 3-5 years ago and not meet any exclusion criteria. They will subsequently be eligible for long-term immune response and revaccination according to the study protocol. 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 41 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: CLL patients 1. Patients receiving high dose corticosteroids ( =20 mg Prednisolone) or other immunosuppressive drugs that is not part of active CLL treatment 2. Patients who have had an allergic reaction to any vaccination in the past 3. Patients with a positive DAT (Direct Antiglobulin Test) or known present or previous hemolysis, ITP and Guillain-Barre 4. Patients failing to give informed consent 5. Patients with ongoing immunoglobulin therapy 6. Patients with known HIV infection 7. Patients who have received a pneumococcal vaccine outside the study protocol within the last 12 months 8. Active febrile infection 9. Increased bleeding risk due to severe thrombocytopenia or other coagulopathies that would, in the opinion of the investigator, contraindicate intramuscular injection Controls 1. Serious chronic disorder including chronic obstructive pulmonary disease (COPD) requiring supplemental oxygen treatment, end-stage renal disease, clinically unstable cardiac disease or any other disorder that, in the investigator’s opinion, excludes the subject from participating in the study; 2. Known or suspected immunodeficiency or other conditions associated with immunosuppression including immunoglobulin class/subclass deficiencies with or without substitution treatment, splenectomy in the medical history, generalized malignancy, human immunodeficiency virus (HIV) infection, haematological malignancies, bone marrow or organ transplant in the medical history; 3. Subjects receiving treatment with high dose corticosteroids (=20 mg Prednisolone) or other immunosuppressive drugs, or planned to receive through study participation; 4. Subjects who have had an allergic reaction to any component of PCV13 in the past; 5. Subjects with known present or previous hemolysis, ITP and Guillain-Barre; 6. Subjects failing to give informed consent; 7. Subjects who have received a pneumococcal vaccine after the primary vaccination aproximately 3-5 years ago; 8. Active febrile infection; 1.9. Increased bleeding risk due to severe thrombocytopenia or other coagulopathies that would, in the opinion of the investigator, contraindicate intramuscular injection (for treatment with oral anticoagulation therapy, see section 7.3).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To determine and compare the sustained immune response 3-5 years after vaccination with a single dose of 13-valent pneumococcal conjugated vaccine (PCV13, Prevenar13®) or conventional 23-valent capsular polysaccharide vaccine (PPSV23, Pneumovax®) in the cohort from our previous randomized phase III trial. 2) 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: 1) To determine the prevalence of pneumococcal colonization in nasopharynx. 2) To determine the incidence of invasive pneumococcal disease in the study cohort. 3) To study the effect of pneumococcal revaccination on immune cells and cytokine levels. 4) To compare the sustained immune response between CLL patients and immunocompetent controls, 3-5 years after vaccination with PCV13 and PPSV23. 5) To compare the immune response between CLL patients and immunocompetent controls, after revaccination with one dose of PCV13. 6) To compare the prevalence of pneumococcal colonization and incidence of invasive pneumococcal disease between CLL patients and immunocompetent controls after vaccination and revaccination. 7) To compare the effect of pneumococcal revaccination on immune cells and cytokine levels between CLL patients and immunocompetent controls. 8) To compare the immune response after SARS-CoV-2 vaccination to the immune response after pneumococcal revaccination. ;Primary end point(s): 1) To study the long-term immune response between the two groups 3-5 years after vaccination with PCV13 or PPSV23, measured as the proportion of subjects with a positive vaccination response in each of the two groups. 2) To study the short-term immune response 8 weeks and 16 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To study the persistent immune response after revaccination in terms of OPA titers 12 months after first dose of revaccination compared to the short-term pre- and post-revaccination sera. 2) To compare ELISA GMCs for each serotype measured 3-5 years after initial vaccination. 3) To compare ELISA GMCs for each serotype measured 8 weeks, 16 weeks and 12 months after revaccination. 4) To study the incidence of IPD during the period from the initial vaccination to maximum five years after the first dose of revaccination. 5) To study the incidence of pneumococcal colonization by culturing of nasopharyngeal swabs at inclusion after 8 weeks, 16 weeks and 12 months. 6) To study the long-term immune response (ELISA and OPA) 3-5 years after vaccination with PCV13 or PPSV23, by comparing CLL patients and controls. 7) To study the short-term immune response (ELISA and OPA) 8 weeks after revaccination with one dose of PCV13, by comparing CLL patients and controls. 8) To study the additive immune response (ELISA and OPA) after a second revaccination dose (PCV13 or PPSV23) of CLL patients in comparison with controls with no second revaccination dose, 16 weeks and 12 months after revaccination. 9) To study the immune response 3-4 weeks, 6-8 weeks, 6 months and 12 months after initial SARS-CoV-2 vaccination in terms of antibody titers/function induced by the vaccine and compare to the immune response after pneumococcal revaccination. ;Timepoint(s) of evaluation of this end point: PCV13 or PPSV23 vaccination: 8 weeks, 16 weeks and 12 months after revaccination. Covid-19 vaccination: 3-4 weeks after each dose and 6 and 12 months after the first Covid-19 vaccination. | — |
Countries
Sweden
Contacts
Public ContactDept of Medicine, Hematology
Region Örebro län
Outcome results
None listed