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

May 17, 2021 updated by: University Hospital, Tours

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

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%).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
- 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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
- 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.
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)
During the two weeks after both vaccines injection
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)
During all the study (one year for each patient)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Tours

Collaborators

Hôpital Cochin

Investigators

  • Study Director: ZOHA MAAKAROUN-VERMESSE, MD-PHD, University Hospital of Tours

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 3, 2020

Primary Completion (Anticipated)

July 3, 2021

Study Completion (Anticipated)

July 3, 2022

Study Registration Dates

First Submitted

December 24, 2019

First Submitted That Met QC Criteria

December 30, 2019

First Posted (Actual)

January 2, 2020

Study Record Updates

Last Update Posted (Actual)

May 18, 2021

Last Update Submitted That Met QC Criteria

May 17, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DR190111-EVAPOR
  • 2019-002542-20 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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