Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05145101 |
| Other study ID # |
W20_197#20.228 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 7, 2020 |
| Est. completion date |
March 31, 2022 |
Study information
| Verified date |
December 2021 |
| Source |
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
| Contact |
Hannah Garcia Garrido, MD |
| Phone |
+31205663800 |
| Email |
h.m.garciagarrido[@]amsterdamumc.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
In this study the antibody response after vaccination with the 13-valent pneumococcal
conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine
(PPSV23) in adults with chronic lymphocytic leukemia will be investigated.
Description:
Background Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of both
invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by
Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal
vaccination for all CLL patients, preferably before initiation of treatment. The recommended
vaccination schedule consists of Prevenar13®, a 13-valent pneumococcal conjugated vaccine
(PCV13) followed 2 months later by Pneumovax23, a 23-valent polysaccharide vaccine (PPSV23).
The immunological efficacy of this sequential vaccination schedule in CLL patients is
unknown. Previous studies have only investigated responses to either PCV13 or PPSV23 alone.
Responses to PPSV23 alone are poor in CLL patients. Responses to the 7-valent pneumococcal
conjugated vaccine (PCV7) or PCV13 are higher compared to responses to PPSV23, but lower
compared to responses in healthy individuals. More advanced disease stage and lower baseline
IgG negatively influence responses to vaccination.
The aim of this observational cohort study is to assess the immunogenicity of the currently
recommended vaccination schedule of PCV13 followed by PPSV23 in CLL patients.
2. Methods Study design and population As part of routine care, all adult CLL patients naïve
to pneumococcal vaccination and cared for in the Amsterdam UMC-location AMC, Flevoziekenhuis,
HagaZiekenhuis, Elisabeth-TweeSteden Hospital, Noordwest Ziekenhuisgroep, Albert Schweitzer
Hospital and Ikazia Hospital receive one dose of Prevenar13® followed by one dose of
Pneumovax23® 2 months later. According to the current local standard of care for
immunosuppressed individuals, the response to vaccination will be assessed by measuring
pneumococcal antibody levels before and 4-8 weeks after vaccination.
After obtaining informed consent clinical data will be collected by a trained medical
student, nurse or research assistant according to a standardized electronic case report form
(Castor EDC). Variables included in the case report form are: age, sex, smoking behaviour,
Rai stage (I/II/III), past or ongoing chemotherapy, ongoing steroid treatment, past or
ongoing therapy with a monoclonal anti-CD20 antibody (and date of last infusion), baseline
total IgG level, baseline lymphocyte count, baseline haemoglobin level, baseline platelet
level, baseline pneumococcal IgG levels, post-vaccination pneumococcal IgG levels, date of
PCV and PPSV23 vaccine administration, date of antibody measurements, comorbidities (Charlson
comorbitiy index).
Laboratory methods and definitions Serotype-specific pneumococcal immunoglobulin G (IgG)
concentrations to 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F)
and 4 serotypes unique to PPSV23 (8, 15B, 20, 33F) will be determined in the immunology
laboratory of the UMC Utrecht. A validated multiplex immunoassay will be used (Luminex®
technology). Serologic response will be defined as a ≥4-fold increase in serotype specific
anti-pneumococcal IgG for ≥70% of measured. Serologic protection will be defined as an
antibody concentration ≥1.3 mcg/ml for ≥70% of all measured serotypes, according to the
definition of the American Academy of Allergy, Asthma & Immunology. In addition, because most
previous studies used the WHO cut-off for protection in infants (≥0.35mcg/ml) data will also
be analyzed by the infant correlate of protection to be able to compare the results with
previous studies.
