Clinical Trial Assessing the Immunogenicity of an Anti-pneumococcal Vaccination Strategy (PCV13+PPV23 Versus PREVENAR20) in Adult Patients Treated for a Lymphoma

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorPoitiers University Hospital

About this trial

The French Public Health Council recommended pneumococcal vaccination combined strategy for all immunocompromised patients in 2012. This strategy consisted in conjugated 13-valent pneumococcal (PCV13) injection followed 2 months later by polysaccharide 23-valent (PPV23) vaccine injection. In 2024, Health authorities changed guidelines to recommend one injection of PREVENAR20 instead of the 2-vaccine scheme general practitioners are usually in charge of this vaccination. Conjugated pneumococcal vaccine enhances the immunogenicity of the polysaccharide vaccine. Acute leukemia and lymphoma are treated with multiple courses of chemotherapy, impairing the immune system and potentially the response to vaccination. These patients are more at risk for developing pneumococcal invasive diseases than the general population. However, efficacy of pneumococcal vaccination is poorly documented in this setting. We assume that 65% of the patients are non-responders to double compared to 45% for PCV20PREVENAR20 vaccination, according to their anti-pneumococcal immunoglobulin G (Ig) titers and the opsonophagocytic activity (OPA). To assess the immunogenicity of the pneumococcal vaccination combined strategy in adult population of acute leukemia and lymphoma, we will measure anti-pneumococcal serotype-specific IgG titers and OPA at different time-points after completion of the combined vaccine strategy. The primary objective is to assess the immunogenicity of pneumococcal vaccination combined strategy at 3 months after the PCV13 injection (corresponding to 1 month after the end of the combined strategy in cohort A) using Ig G titers and OPA, compared to 3 months post PREVENAR20 (cohort B). At different time points (day 0, 4 weeks post PCV13, and 4 weeks, 3-6 months and 9-12 months post PPV23 and in day 0, 4 weeks post PREVENAR20 and 3 months, 5-8 months and 11-14 months post PREVENAR20, the immunological response to vaccination will be monitored using specific-serotype IgG titers, OPA, and total anti-pneumococcal Ig. We will determine predictive factors of non-response to vaccination by comparing demographic data, biological data and treatment received lymphoma patients. The tolerance and safety of the vaccination strategy will also be assessed in this specific hematological population.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient ≥ 18 year-old.

AND medical follow-up in hematology unit

AND had received a first course of chemotherapy for diffuse large B cell lymphoma or for follicular lymphoma

Life expectancy > 6 months.

Disqualifiers

Receiving monoclonal antibodies or biotherapies altering the immune response, other than anti-CD20 antibodies in the chemotherapy protocol.

Uncontrolled bacterial, viral or fungal infection less than 7 days.

Previous vaccination with PCV13 or PPV23 (unless PCV13 was administered in childhood. The last injection must be performed at least five years ago).

Preexisting condition that altered the immune response: splenectomy, HIV, primary or secondary immune deficiency, nephrotic syndrome, sickle cell anemia, autoimmune disorder, solid organ transplantation, immunosuppressive drugs or biotherapy not included in the chemotherapy.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Prevenar 13 + Pneumovax 23

    Biological/Vaccine

    Cohort study A before modification of vaccination national guidelines

  • PREVENAR20

    Biological/Vaccine

    Health authorities changed guidelines to recommend one injection of PREVENAR20 instead of the 2-vaccine scheme general practitioners are usually in charge of this vaccination. Cohort study B

Treatment groups

160 Participants
are divided into 2 treatment groups
Group A: Cohort study AOther 1 intervention
Group B: Cohort study BOther 1 intervention

Trial outcomes

Primary outcomes

1

Proportion of patients having an immunological response

Proportion of patients having an immunological response to combined strategy at 4 weeks after the end of the combined strategy compared to proportion of patients having an immunologicalresponse at 3 months post PREVENAR20 injection. An immunological response to vaccination is defined by 7/10 tested serotypes responding to these 4 criteria: a serotype-specific IgG titer ≥ 1,3 μg/mL (WHO threshold), a two-fold increase of this IgG titer compare to baseline before vaccination, a serotype-specific OPA ≥1/8, and a four-fold increase of functional antibodies compare to baseline.

Time frame
4 weeks after the end of the combined strategy for cohort study A and 3 months post injection for cohort study B

Secondary outcomes

1

Proportion of patients having an ELISA serotype-specific IgG titer and a two-fold increase of this IgG titer

Proportion of patients having an ELISA serotype-specific IgG titer ≥ 1.3 μg/mL (WHO threshold) and a two-fold increase of this IgG titer compared to baseline at 4 weeks after the PCV13 or PREVENAR20 injection

Time frame
4 weeks after injection
2

Proportion of patients having a sustainable response to vaccination

Proportion of patients having a sustainable response to vaccination defined by an ELISA serotype-specific IgG titer ≥ 1μg/mL (WHO threshold) and a two-fold increase of this IgG titer compared to baseline between 3-6 months after the PPV23 injection or 5-8 months post PREVENAR20.

Time frame
3-6 months after the PPV23 injection or 5-8 months post PREVENAR20
3

Proportion of patients having a sustainable response to vaccination

Proportion of patients having a sustainable response to vaccination defined by the same criteria as the primary outcome and measured between 9-12 months after the PPV23 injection or 11-14 months post PREVENAR20.

Time frame
9-12 months after the PPV23 injection or 11-14 months post PREVENAR20.
4

Proportion of responding patients having titers of IgG, IgG2, IgM, and IgA rising significantly

Proportion of responding patients having titers of IgG, IgG2, IgM, and IgA rising significantly at 4 weeks after PCV13 or PREVENAR20 injection, and 4 weeks, 3-6 months and 9-12 months after PPV23 injection versus respectively 3 months, 5-8 months and 11-14 months after PREVENAR20 injection. A significant increase is defined by a 4-fold increase of IgG and IgG2 titers, a 13-fold increase of IgA titers, and a 20-fold increase of IgM titers compared to baseline at inclusion.

Time frame
4 weeks after PCV13 or PREVENAR20 injection, and 4 weeks, 3-6 months and 9-12 months after PPV23 injection versus respectively 3 months, 5-8 months and 11-14 months after PREVENAR20 injection.

Other outcomes

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