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

Immunogénicité de la Vaccination Anti-pneumococcique (PCV13+PPV23 Versus PREVENAR20) Dans le Lymphome Chez l'Adulte

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, Non-Hodgkin; Vaccine; Streptococcus Pneumoniae
• Intervention / Treatment: Biological: Prevenar 13 + Pneumovax 23; Biological: PREVENAR20

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mathieu Puyade, MD, PhD; Phone Number: 0033 5 49 44 32 76; Email: mathieu.puyade@chu-poitiers.fr
• Study Contact Backup: Name: Fanny Abriat; Phone Number: 0033 5 49 44 37 96; Email: fanny.abriat@chu-poitiers.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • CHU Angers
    • Contact: Mathilde HUNAULT, Pr
  • Bordeaux, France
    • Recruiting
    • CHU Bordeaux
    • Contact: François-Xavier GROS, Dr
  • Limoges, France
    • Recruiting
    • CHU Limoges
    • Contact: Arnaud JACCARD, Pr
  • Nantes, France
    • Recruiting
    • CHU Nantes
    • Contact: Pierre PETERLIN, Dr
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Contact: Maria Pilar GALLEGO HERNANZ, Dr
  • Périgueux, France
    • Recruiting
    • CH Périgueux
    • Contact: Claire CALMETTES, Dr
  • Tours, France
    • Recruiting
    • CHU Tours
    • Contact: Antoine MACHET, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• Negative pregnancy test.
• Having signed the consent form.
• Having an health insurance.

Exclusion Criteria:

• 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.
• Patient who already received chemotherapy for malignancy in the previous 2 years before the inclusion.
• Major blood clotting disorders preventing intramuscular injection.
• Medical history of anaphylactic reaction to vaccination.
• Known allergy to one of the vaccine components.
• Involvement to another vaccine biomedical research.
• Protected person.
• Pregnant women or women of childbearing age without appropriate contraceptive measures.
• Perfusion of polyvalent immunoglobulins during follow-up.
• Participants with hypersensitivity to aluminum phosphate, phenol or CRM197 protein, protein derived from Corynebacterium diphtheria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort study A; 80 patients already included in study cohort A. They received an injection of 13-valent conjugate vaccine (PCV13), followed by an injection of 23-valent polysaccharide vaccine (PPV23) at least 2 months later.	Biological: Prevenar 13 + Pneumovax 23; Cohort study A before modification of vaccination national guidelines
Other: Cohort study B; 80 patients to be included in study cohort B. They will receive a single injection of PREVENAR20 vaccine.	Biological: PREVENAR20; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks after the end of the combined strategy for cohort study A and 3 months post injection for cohort study B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	4 weeks after injection
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.	3-6 months after the PPV23 injection or 5-8 months post PREVENAR20
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.	9-12 months after the PPV23 injection or 11-14 months post PREVENAR20.
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.	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.
Predictive factors for non-response to vaccination	To determine predictive factors for non-response to vaccination at 4 weeks, and 9-12 months after PPV23 versus respectively 3 months and 11-14 months after PREVENAR20 injection such as age, immune status, chemotherapy, immunotherapy.	4 weeks, and 9-12 months after PPV23 versus respectively 3 months and 11-14 months after PREVENAR20 injection
Local or general reactions to vaccination and invasive pneumococcal infections	Number of patients having local or general reactions to vaccination and number of invasive pneumococcal infections with a documented serotype considered as vaccination failure.	14 months
Concordance between the reference immuno-monitoring dosage and another kit of dosage	To assess the concordance between the reference immuno-monitoring dosage (WHO ELISA) and another kit of dosage (Vacczyme® Binding Site®).	14 months

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Pneumonia; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Pneumococcal Infections; Pneumonia, Bacterial; Lymphoma; Lymphoma, Non-Hodgkin; Pneumonia, Pneumococcal; Immunologic Factors; Physiological Effects of Drugs; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: HEMATOVAC; 2024-517288-22-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No