Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma (HEMATOVAC)

Immunogénicité de la Vaccination Anti-pneumococcique Dans la leucémie aiguë et 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 injection followed 2 months later by polysaccharide 23-valent vaccine injection. 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 70% of the patients are non-responders to vaccination, according to their anti-pneumococcal immunoglobulin G titers and the opsonophagocytic activity. To assess the immunogenicity of the pneumococcal vaccination combined strategy in adult population of acute leukemia and lymphoma, the investigator will measure anti-pneumococcal serotype-specific immunoglobulin G titers and opsonophagocytic activity 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 13-valent pneumococcal injection (corresponding to 1 month after the end of the combined strategy) using immunoglobulin G titers and opsonophagocytic activity. At different time points (day 0, 1 month after the 13-valent pneumococcal injection, the day of the injection of the polysaccharide 23-valent vaccine, one month after the injection of the polysaccharide 23-valent vaccine, 3-6 months after the polysaccharide 23-valent vaccine,9-12 months after the polysaccharide 23-valent vaccine), the immunological response to vaccination will be monitored using specific-serotype immunoglobulin G titers, opsonophagocytic activity, and total anti-pneumococcal Immunoglobulin. The investigator will determine predictive factors of non-response to vaccination by comparing demographic data, biological data and treatment received by both acute myeloblastic leukemia and 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; Acute Myeloid Leukemia; Vaccine; Streptococcus Pneumoniae
• Intervention / Treatment: Drug: Prevenar13 Pneumo-23

• 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 Perigueux
    • 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 except demethylating for acute myeloblastic leukemia without ProMyelogenousLeukemia-RetinoicAcidReceptor alpha and no planned allogeneic hematopoietic stem cell transplantation (anti-IDH treatment authorized) or for diffuse large B cell lymphoma or for follicular lymphoma
• Life expectancy > 6 months
• Having signed the consent form
• Having an health insurance

Exclusion Criteria:

• Receiving monoclonal antibodies or biotherapies altering the immune response, other than anti-Cluster of differentiation number 20 antibodies in the chemotherapy protocol.
• Uncontrolled bacterial, viral or fungal infection less than 7 days
• Previous vaccination with 13-valent pneumococcal vaccine or polysaccharide 23-valent vaccine (unless 13-valent pneumococcal vaccine 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
• Allogeneic hematopoietic stem cell transplantation planned in the following 3 months after the first chemotherapy course
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Vaccination; All patients will be vaccinated according to national guidelines	Drug: Prevenar13 Pneumo-23; Vaccination according national guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients having a good response to combined strategy	Proportion of patients having a good response to combined strategy at 4 weeks after the end of the combined strategy. A good response to vaccination is defined by 4/7 tested serotypes responding to these 4 criteria: a serotype-specific immunoglobulin G titer ≥ 1μg/L (WHO threshold), a two-fold increase of this immunoglobulin G titer compare to baseline before vaccination, a serotype-specific opsonophagocytic activity ≥1/8, and a four-fold increase of functional antibodies compare to baseline.	39 months

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

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 (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

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

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