Prevnar13 in Pneumococcal Infections and Chronic Lymphocytic Leukemia and Vaccine-Preventable Diseases - Clinical Trials Registry

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Biological: Prevnar13

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 Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Hannah Garcia Garrido, MD
Phone Number: +31205663800
Email: h.m.garciagarrido@amsterdamumc.nl

Study Locations

Netherlands
- - Amsterdam-Zuidoost, Netherlands, 1105 AZ
    - Recruiting
    - Amsterdam UMC Locatie AMC
    - Contact:
      
      Hannah Garcia Garrido, MD
      
      Phone Number: 0031205663800
      
      Email: h.m.garciagarrido@amsterdamumc.nl
    - Principal Investigator:
      
      Koen de Heer, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

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

Description

Inclusion Criteria:

CLL
Age >17
Naive to pneumococcal vaccination

Exclusion Criteria:

Not able/willing to participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hannah Garcia Garrido

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2020

Primary Completion (Anticipated)

March 31, 2022

Study Completion (Anticipated)

March 31, 2022

Study Registration Dates

First Submitted

November 18, 2021

First Submitted That Met QC Criteria

December 1, 2021

First Posted (Actual)

December 6, 2021

Study Record Updates

Last Update Posted (Actual)

December 20, 2021

Last Update Submitted That Met QC Criteria

December 3, 2021

Last Verified