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Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab (EVAPOR)

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ClinicalTrials.gov Identifier: NCT04214444
Recruitment Status : Recruiting
First Posted : January 2, 2020
Last Update Posted : May 18, 2021
Sponsor:
Collaborator:
Hôpital Cochin
Information provided by (Responsible Party):
University Hospital, Tours

Brief Summary:
Pneumococcal infections remain frequent and potentially fatal. To prevent them, two anti-pneumococcal vaccines exist: a 13-valent conjugate vaccine (Prevenar®) and a 23-valent polysaccharide vaccine (Pneumovax®). For their utilization, several studies approved a prime-boost strategy. It consist two administer Pneumovax® at least two months later than Prevenar®. Patients with diffuse large B-cell Lymphoma (DLBCL) have a higher-risk to develop a pneumococcal infection. The main reason is immunosuppression, induced by rituximab (B cell depletion), chemotherapy and lymphoma. Patients are treated by immunochemotherapy, combining rituximab (anti-CD20 monoclonal antibody) and conventional chemotherapy (CHOP). However, those patients have a low rate of vaccination (about 15%).

Condition or disease Intervention/treatment Phase
Pneumococcal Infections Lymphoma, Large B-Cell, Diffuse Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma Phase 3

Detailed Description:

Pneumococcal infections remain frequent and potentially fatal. To prevent them, two anti-pneumococcal vaccines exist: a 13-valent conjugate vaccine (Prevenar®) and a 23-valent polysaccharide vaccine (Pneumovax®). For their utilization, several studies approved a prime-boost strategy. It consist two administer Pneumovax® at least two months later than Prevenar®. Patients with diffuse large B-cell Lymphoma (DLBCL) have a higher-risk to develop a pneumococcal infection. The main reason is immunosuppression, induced by rituximab (B cell depletion), chemotherapy and lymphoma. Patients are treated by immunochemotherapy, combining rituximab (anti-CD20 monoclonal antibody) and conventional chemotherapy (CHOP). However, those patients have a low rate of vaccination (about 15%). Also, in the current literature, rare studies investigated prime-boost immunogenicity in this relevant population. The investigators will evaluate vaccinal response of 10 serotype-specific immunoglobulin G (1, 3, 4, 6B, 7F, 9V, 14, 18C, 19F, 23F) at different time of treatment.

The investigators search to compare efficiency of prime-boost anti-pneumococcal vaccination according to the time of prevenar administration (before or after immunochemotherapy) and to the dose of Prevenar® (single or double-dose).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab (EVAPOR Study)
Actual Study Start Date : July 3, 2020
Estimated Primary Completion Date : July 3, 2021
Estimated Study Completion Date : July 3, 2022


Arm Intervention/treatment
Active Comparator: Single-dose before treatment
12 patients will receive a single-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection
Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma
The investigators aim to describe efficiency and tolerability of prime-boost vaccination against pneumococcus in patients with Diffuse large B-cell Lymphoma. The investigators search to evaluate immunogenicity of prime-boost depending on the time of prevenar administration (before or after immunochemotherapy) and on the dose (single or double dose).

Active Comparator: Single-dose after treatment
12 patients will receive a singe-dose of prevenar three weeks after the beginning of the immunochemotherapy (R-CHOP) following two months later by pneumovax injection
Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma
The investigators aim to describe efficiency and tolerability of prime-boost vaccination against pneumococcus in patients with Diffuse large B-cell Lymphoma. The investigators search to evaluate immunogenicity of prime-boost depending on the time of prevenar administration (before or after immunochemotherapy) and on the dose (single or double dose).

Experimental: Double-dose before treatment
12 patients will receive a double-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection.
Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma
The investigators aim to describe efficiency and tolerability of prime-boost vaccination against pneumococcus in patients with Diffuse large B-cell Lymphoma. The investigators search to evaluate immunogenicity of prime-boost depending on the time of prevenar administration (before or after immunochemotherapy) and on the dose (single or double dose).




Primary Outcome Measures :
  1. Proportion of responder patients at the end of treatment. [ Time Frame: - day of Prevenar® administration, - day of Pneumovax® injection (2 months after Prevenar® injection) - six weeks after Pneumovax® injection - 1 month after last R-CHOP cycle, - at six months after end of treatment. ]
    The response to a specific serotype was defined as both a 2-fold increase of pneumococcal IgG antibody level (ELISA) between baseline and end of treatment (one month after last RCHOP cycle) and an antibody level >= 1µg/mL. at end of treatment.


Secondary Outcome Measures :
  1. Rates of responders patients to each serotype as assessed by opsonophagocytosis [ Time Frame: - day of Prevenar® administration, - day of Pneumovax® injection (2 months after Prevenar® injection) - six weeks after Pneumovax® injection - 1 month after last R-CHOP cycle, - at six months after end of treatment. ]
    response to a specific serotype was defined by both at least a fourfold increase of the opsonization index (OI, defined by the serum dilution killing 50% of the bacterial inoculum) between baseline and end of treatment.

  2. Tolerance of the double-dose compared to single dose of Prevenar® [ Time Frame: During the two weeks after both vaccines injection ]
    Presence of local and/or systemic reaction detailed on a questionary (fever, headache, fatigue, chills, rash, muscle pain, joint pain)

  3. Clinical efficiency [ Time Frame: During all the study (one year for each patient) ]
    Pneumococcal documented infection during treatment (pneumonia, meningitis, acute media otitis, bacteremia) with proof of pneumococcal presence (on blood cultures, chest radiography, other samples)



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • De novo Diffuse Large B-Cell Lymphoma diagnostic (according 2016 World Health Organization (WHO) classification)
  • Treatment decision by immunochemotherapy (R-CHOP)
  • Age over 18 years old
  • Negative pregnancy test at inclusion
  • Active contraception at inclusion
  • Free and informed consent procedure at inclusion
  • Affiliation of the social security system

Exclusion Criteria:

  • Patient with prior treatment by immunotherapy or chemotherapy
  • Patient with prior treatment by debulking chemotherapy (COP)
  • Patient with prior treatment by high-dose of corticosteroids
  • Patients with an autoimmune disease
  • Patients with a diffuse large B-cell lymphoma from transformation (follicular lymphoma, chronic lymphoid leukemia)
  • Immunosuppressed patient with : asplenia, hereditary immunodeficiency disorder, infection by HIV, hepatitis B or C viruses, transplanted patient, hematopoietic stem cell transplantation, nephrotic syndrome, meningeal breach, cochlear implants.
  • Patients vaccinated in the last month before inclusion
  • Patients with prior transfusion of blood-products or immunoglobulins in the last three months before inclusion
  • Patient with bleeding disorders or thrombopenia contraindicating intramuscular injection
  • Patient with prior pneumococcal documented infection
  • Patient with current pregnancy and/or breastfeeding
  • Patient under curatorship or guardianship

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04214444


Contacts
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Contact: ZOHA MAAKAROUN-VERMESSE, MD-PHD +33247478767 Z.MAAKAROUN-VERMESSE@chu-tours.fr
Contact: Thomas CHALOPIN tomchalopin@gmail.com

Locations
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France
GYAN Recruiting
Tours, France, 37044
Contact: Emmanuel GYAN, MD-PhD       e.gyan@chu-tours.fr   
Sponsors and Collaborators
University Hospital, Tours
Hôpital Cochin
Investigators
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Study Director: ZOHA MAAKAROUN-VERMESSE, MD-PHD University Hospital of TOURS
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Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT04214444    
Other Study ID Numbers: DR190111-EVAPOR
2019-002542-20 ( EudraCT Number )
First Posted: January 2, 2020    Key Record Dates
Last Update Posted: May 18, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Tours:
Lymphoma
pneumococcal vaccination
prime-boost
rituximab
Additional relevant MeSH terms:
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Pneumococcal Infections
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs