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CLLPhase 4NCT05316831

Immune Response After Pneumococcal Vaccination in Patient With Chronic Lymphocytic Leukemia

A Phase 4 study testing PCV13 and PPSV23 in people with CLL and Vaccine Response, run by Region Örebro County at 1 site in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
CLL, Vaccine Response
What is being tested?
PCV13 and PPSV23
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
1 siteSweden
Study dates
1 Jan 2019to 1 Oct 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Patients receiving high dose corticosteroids ( ≥20 mg Prednisolone) or other immunosuppressive drugs that is not part of active CLL treatment (criteria for inclusion after discontinuing high dose corticosteroid treatment, see section 7.3)
  • 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
Show all 9Show fewer
  • 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) -

Trial locations and contacts

1 site in 1 country.

Sweden1 site

  • Magdalena Kättström

    Örebro

Other trials in Sweden

About this study

Official title: Long Term Effect on Immune Response After Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukemia and Evaluation of the Effect of Revaccination

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.

Read the detailed description

Chronic lymphocytic leukemia (CLL) patients have increased risk of pneumococcal infection due to defect T-cells, complements and neutrophil/monocyte function or hypogammaglobulinaemia. Side effects of different treatment modalities add further risk of infection.

Two pneumococcal vaccines are available, non-conjugated pneumococcal polysaccharide vaccines (PPSVs) and protein-conjugated vaccines (PCVs). 23-valent Pneumovax (PPSV23) has been recommended for healthy adults to protect against invasive pneumococcal disease (IPD) in Sweden and other countries for >30 years. Patients with reduced adaptive immune function respond inadequately to PPSVs. Instead, the 13-valent Prevenar (PCV13) is recommended for a thymus-dependent immunological memory, yielding increased and persistent immune response .

In 2016, Swedish recommendations on pneumococcal vaccination of risk groups were updated, recommending PCV13 plus PPSV23 after >8 weeks, but only after individual assessment. The evidence in CLL patients is limited but the Swedish CLL-Group has adopted the recommendations. The two vaccines are administrated consecutively to broaden the protection of additional serotype. If previously PPSV23 vaccinated, the PCV13 should be given >12 months after PSV23 to avoid decreasing antibodies, i.e hyporesponse, but this is not studied in CLL patients.

Between 2013-2016, the investigators conducted a phase III trial at 8 hematological clinics in Sweden, including 126 untreated CLL patients, randomized to PCV13 (n=63) or PPSV23 (n=63) . The immune response was analyzed in terms of antibody induction and functionality, measured by enzyme-linked immunosorbent assay (ELISA) and opsonophagocytosis assay (OPA), respectively. The proportion of responding patients was larger for PCV13 than for PPSV23 after 4 weeks (40% vs. 22%, p=0.03) and 6 months (33% vs. 17%, p=0.04).

This study aims to investigate the persistent antibody protection in CLL patients 4-6 years after vaccination with PCV13 (n=63) vs PPSV23 (n=63), and the effect of revaccination with PCV13 in both groups. Also, the aim is to study if a repeated dose of PCV13 results in improved response, similar to controls after one dose of PCV13, and compared to PCV13 plus PPSV23 revaccination. Secondly, the study investigates the effect of pneumococcal vaccination on incidence of pneumococcal infection and colonization. A control group (N=32) has been included. Peripheral blood mononuclear cell (PBMC) have been collected and further studies on the dynamics of immune cells and cytokines before and after primary immunization and revaccination with polysaccharide vaccines and conjugated vaccines will be investigated.

A sub study was initiated february 2021 in the same cohort for sampling after vaccination against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the same study cohort, enabling comparison of immune response after administrating mRNA (messenger ribonucleic acid) vaccines.

Being tested
PCV13, PPSV23

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PCV13Biological

    Also called Prevenar13

    Pneumococcal polysaccharides conjugated to CRM197 carrier protein

  • PPSV23Biological

    Also called Pneumovax23

    Pneumococcal polysaccharides

Study groups in NCT05316831
Study groupRoleWhat they receive
Group AExperimentalGroup A CLL patients: Previously immunized with PCV13, in this study receiving PCV13 followed by PPSV23
Receives: Biological: PCV13; Biological: PPSV23
Group BExperimentalGroup B CLL patients: Previously immunized with PPSV23, in this study receiving PCV13 followed by PCV13
Receives: Biological: PCV13
Group CActive comparatorGroup C controls: Previously immunized with PCV13, in this study receiving PCV13
Receives: Biological: PCV13
Group DActive comparatorGroup C controls: Previously immunized with PPPSV23, in this study receiving PCV13
Receives: Biological: PCV13

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3-5 years after vaccination

  2. 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.

    Measured: Before and 8, 16 and 52 weeks after first revaccination

Secondary outcomes (6)

  1. Prevalence of pneumococcal colonization

    To study the incidence of pneumococcal colonization by naso-pharyngeal culturing nasopharyngeal swabs at inclusion after 8 weeks, 16 weeks and 12 months.

    Measured: Before and 8, 16 and 52 weeks after first revaccination

  2. Effect of pneumococcal revaccination on T- and B-cell subsets

    Dynamics of T- and B-cell subsets before and after revaccination will be explored using flow cytometry to determine the proportions of different B- and T-cell subsets

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

  3. Antibody response after vaccination with PPSV23, PCV13 and mRNA vaccine

    Antibody titers measured with FMIA regarding pneumococcal antibodies and Diasorins SARS-CoV-2 TrimericS IgG test (COV2TG) regarding Covid-19 antibodies, comparing antibody response to polysaccharide vaccine, conjugated vaccine and mRNA vaccine

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

  4. Incidence of invasive pneumococcal disease (IPD)

    To determine the incidence of IPD among the study participants by collecting data from medical records

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

  5. Effect of pneumococcal revaccination on cytokine levels

    Investigate the dynamics of cytokine levels before and after revaccination determined by multiplex immunoassays

    Measured: Before and 8, 16 and 52 weeks after first revaccination

  6. Immune cell response after vaccination with PPSV23, PCV13 and mRNA vaccine

    Dynamic of T- and B-cell subsets before and after vaccination with polysaccharide vaccine, conjugated vaccine and mRNA vaccine using flow cytometry

    Measured: Before, 4-8 weeks afte0r every vaccination and 12 month after first pneumococcal revaccination and second mRNA vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2022
  2. Study start1 Jan 2019
  3. Primary completion30 Jun 2021
  4. Study completion1 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05316831
Sponsor's protocol ID
234041
Status last verified
Mar 2023
First submitted
26 Sep 2021
Last updated
30 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 40045895

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing PCV13 and PPSV23 in people with CLL and Vaccine Response, run by Region Örebro County at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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®) (time frame: 3-5 years after vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05316831, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.

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