Clinical trial NCT05145101: Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia
Official title: Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Chronic Lymphocytic Leukaemia.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pneumococcal Infections
Chronic Lymphocytic Leukemia
Vaccine-Preventable Diseases
Invasive Pneumococcal Disease, Recurrent Isolated
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2021-12-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: As part of routine care, all adult CLL patients naïve to pneumococcal vaccination must 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

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* CLL
* Age \>17
* Naive to pneumococcal vaccination

Exclusion Criteria:

* Not able/willing to participate

Primary outcomes:
measure: serologic response rate
timeFrame: 1-2 months after vaccination schedule
Secondary outcomes:
measure: Serologic protection rate
timeFrame: 1-2 months after vaccination
measure: Geometric mean concentrations of serotype specific anti-pneumococcal IgG for 9 pneumococcal serotypes
timeFrame: Month 0, month 4
Other outcomes:
Locations:
city: Amsterdam-Zuidoost
country: Netherlands
facility: Amsterdam UMC Locatie AMC
Study officials:
References: