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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Prevenar 13 + Pneumovax 23
  Cohort study A before modification of vaccination national guidelines
• Биопрепарат 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

Первичные конечные точки

• Proportion of patients having an immunological response [Срок оценки: 4 weeks after the end of the combined strategy for cohort study A and 3 months post injection for cohort study B]

Вторичные конечные точки (7)

• Proportion of patients having an ELISA serotype-specific IgG titer and a two-fold increase of this IgG titer [Срок оценки: 4 weeks after injection]
• Proportion of patients having a sustainable response to vaccination [Срок оценки: 3-6 months after the PPV23 injection or 5-8 months post PREVENAR20]
• Proportion of patients having a sustainable response to vaccination [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 14 months]
• Concordance between the reference immuno-monitoring dosage and another kit of dosage [Срок оценки: 14 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 7 центров

• Chu Angers — Angers
• CHU Bordeaux — Bordeaux
• CHU Limoges — Limoges
• Chu Nantes — Nantes
• Ch Perigueux — Périgueux
• CHU Poitiers — Poitiers
• CHU Tours — Tours

Идентификаторы

NCT: NCT04460235 · HEMATOVAC · 2024-517288-22-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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