Immune Response After Pneumococcal Vaccination in Patient With Chronic Lymphocytic Leukemia

NCT05316831 | Completed Phase 4 DMC

• 1 other identifier: 234041
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, multi-centre trial was conducted between 2013-2016, including 128 patients with untreated CLL from eight hematological clinics in Sweden. Vaccination with polysaccharide pneumococcal vaccine (PPSV23) or conjugated pneumococcal vaccine (PCV13) was performed and the results were published 2018. PCV13 showed a superior immune response, measured as OPA (opsonophagocytic assays) and ELISA (enzyme-linked immunosorbent assay), compared to PPSV23. Immune cells analyses after primary immunization will be performed. Between 2019-2021 a prospective follow up study was conducted of the same cohort and also included a control group. The study participants have been revaccinated with pneumococcal vaccines with the aim to evaluate the effect of repeated dose of PCV13. The antibody response (measured as titer with FMIA (fluorescent multiplexed bead-based immunoassay) and antibody function with MOPA (multiplexed opsonophagocytic assay) will be performed. Studies investigating the dynamics of immune cells before and after primary immunization and revaccination will be performed. The study will give important answers about the optimal vaccination strategy in patients with CLL and can improve the vaccination recommendations in immunocompromised patients.

Conditions

CLL; Vaccine Response

Outcome Measures

Primary Outcomes (2)

• Immune response 3-5 years after primary vaccination with a single dose of 13-valent pneumococcal conjugated vaccine (PCV13, Prevenar13®) or conventional 23-valent capsular polysaccharide vaccine (PPSV23, Pneumovax®)

  The long-term immune response, comparing the two vaccines PCV13 and PPSV23, 3-5 years after vaccination, measured as the proportion of subjects with a positive vaccination response in each of the two groups. A positive vaccination response is defined as a post vaccination OPA titer ≥ (LLOQ) in 8 of the 12 serotypes common for PCV13 and PPSV23 in serum collected

  3-5 years after vaccination

• Change in immune response after revaccination.

  The change in immune response 8,16 and 52 weeks after first revaccination with PCV 13 (followed by a second revaccination, 8 weeks after first revaccination, with either PPSV23 (group A) or PCV13 (group B). Immune response is measured as the proportion of subjects with a positive vaccination response pre- and post- revaccination.

  Before and 8, 16 and 52 weeks after first revaccination

Secondary Outcomes (6)

• Prevalence of pneumococcal colonization

  Before and 8, 16 and 52 weeks after first revaccination

• Effect of pneumococcal revaccination on T- and B-cell subsets

  Before, 7 days and 8 weeks after every revaccination. Twelve months after first revaccination

• Antibody response after vaccination with PPSV23, PCV13 and mRNA vaccine

  Before, 4-8 weeks after every vaccination and 12 months after first pneumococcal revaccination and second mRNA vaccination

• Incidence of invasive pneumococcal disease (IPD)

  From the initial vaccination to maximum five years after the first dose of revaccination

• Effect of pneumococcal revaccination on cytokine levels

  Before and 8, 16 and 52 weeks after first revaccination

Study Arms (4)

Group A

EXPERIMENTAL

Group A CLL patients: Previously immunized with PCV13, in this study receiving PCV13 followed by PPSV23

Biological: PCV13; Biological: PPSV23

Group B

EXPERIMENTAL

Group B CLL patients: Previously immunized with PPSV23, in this study receiving PCV13 followed by PCV13

Biological: PCV13

Group C

ACTIVE COMPARATOR

Group C controls: Previously immunized with PCV13, in this study receiving PCV13

Biological: PCV13

Group D

ACTIVE COMPARATOR

Group C controls: Previously immunized with PPPSV23, in this study receiving PCV13

Biological: PCV13

Interventions

PCV13 BIOLOGICAL

Pneumococcal polysaccharides conjugated to CRM197 carrier protein

Also known as: Prevenar13

Group A; Group B; Group C; Group D

PPSV23 BIOLOGICAL

Pneumococcal polysaccharides

Also known as: Pneumovax23

Group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients who have had an allergic reaction to any vaccination in the past
• Patients with a positive DAT (Direct Antiglobulin Test) or known present or previous hemolysis, ITP (immune thrombocytopenia) and Guillain-Barre
• Patients failing to give informed consent
• Patients with ongoing immunoglobulin therapy
• Patients with known HIV infection
• Patients who have received a pneumococcal vaccine outside the study protocol within the last 12 months
• Active febrile infection
• 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) -

Sponsors & Collaborators

• Region Örebro County: lead

Study Sites (1)

Magdalena Kättström

Örebro, Sweden

Location

Related Publications (1)

• Kattstrom M, Uggla B, Virta C, Melin M, Ekstrom N, Magnuson A, Andersson PO, Hammarlund Y, Lockmer S, Nilsson I, Roth D, Svensson M, Tolf T, Kimby E, Noren T, Athlin S. Revaccination with pneumococcal conjugate vaccine five years after primary immunization improves immunity in patients with chronic lymphocytic leukemia. Haematologica. 2025 Aug 1;110(8):1774-1785. doi: 10.3324/haematol.2024.286942. Epub 2025 Mar 6.

  PMID: 40045895 DERIVED

MeSH Terms

Interventions

13-valent pneumococcal vaccine; 23-valent pneumococcal capsular polysaccharide vaccine

Study Officials

• Bertil Uggla, Md, PhD

  Universitetssjukhuset Örebro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2021
• First Posted: April 7, 2022
• Study Start: January 1, 2019
• Primary Completion: June 30, 2021
• Study Completion: October 1, 2022
• Last Updated: March 30, 2023

Record last verified: 2023-03

Locations

SE (1)