Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia

• Conditions: Vaccine-Preventable Diseases; Pneumococcal Infections; Chronic Lymphocytic Leukemia; Invasive Pneumococcal Disease, Recurrent Isolated

• Registration Number: NCT05145101
• Lead Sponsor: Hannah Garcia Garrido

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.

Study Timeline

• Study Start: 2020-05-07
• Study First Submitted: 2021-11-18
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-01
• Last Update Submitted: 2021-12-03
• Study First Posted: 2021-12-06
• Last Update Posted: 2021-12-20
• Primary Completion: 2022-03-31
• Study Completion: 2022-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• CLL
• Age >17
• Naive to pneumococcal vaccination

Exclusion Criteria

• Not able/willing to participate

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
serologic response rate	1-2 months after vaccination schedule	Proportion of participants with a ≥4-fold increase in serotype specific anti-pneumococcal IgG for ≥6/9 serotypes

Secondary Outcome Measures

Name	Time	Method
Geometric mean concentrations of serotype specific anti-pneumococcal IgG for 9 pneumococcal serotypes	Month 0, month 4
Serologic protection rate	1-2 months after vaccination	Antibody concentration ≥1.3 mcg/ml for ≥6/9 serotypes

Trial Locations

Locations (1)

Amsterdam UMC Locatie AMC; 🇳🇱 Amsterdam-Zuidoost, Netherlands