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

Primary Purpose

Pneumococcal Infections, Lymphoma, Large B-Cell, Diffuse

Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Pneumococcal Infections focused on measuring Lymphoma, pneumococcal vaccination, prime-boost, rituximab

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • GYANRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

Single-dose before treatment

Single-dose after treatment

Double-dose before treatment

Arm Description

12 patients will receive a single-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection

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

12 patients will receive a double-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection.

Outcomes

Primary Outcome Measures

Proportion of responder patients at the 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

Rates of responders patients to each serotype as assessed by opsonophagocytosis
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.
Tolerance of the double-dose compared to single dose of Prevenar®
Presence of local and/or systemic reaction detailed on a questionary (fever, headache, fatigue, chills, rash, muscle pain, joint pain)
Clinical efficiency
Pneumococcal documented infection during treatment (pneumonia, meningitis, acute media otitis, bacteremia) with proof of pneumococcal presence (on blood cultures, chest radiography, other samples)

Full Information

First Posted
December 24, 2019
Last Updated
May 17, 2021
Sponsor
University Hospital, Tours
Collaborators
Hôpital Cochin
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1. Study Identification

Unique Protocol Identification Number
NCT04214444
Brief Title
Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab
Acronym
EVAPOR
Official Title
Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab (EVAPOR Study)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 3, 2020 (Actual)
Primary Completion Date
July 3, 2021 (Anticipated)
Study Completion Date
July 3, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
Collaborators
Hôpital Cochin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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%).
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumococcal Infections, Lymphoma, Large B-Cell, Diffuse
Keywords
Lymphoma, pneumococcal vaccination, prime-boost, rituximab

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-dose before treatment
Arm Type
Active Comparator
Arm Description
12 patients will receive a single-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection
Arm Title
Single-dose after treatment
Arm Type
Active Comparator
Arm Description
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
Arm Title
Double-dose before treatment
Arm Type
Experimental
Arm Description
12 patients will receive a double-dose of prevenar before immunochemotherapy (R-CHOP) following two months later by pneumovax injection.
Intervention Type
Biological
Intervention Name(s)
Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma
Intervention Description
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 Measure Information:
Title
Proportion of responder patients at the end of treatment.
Description
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.
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.
Secondary Outcome Measure Information:
Title
Rates of responders patients to each serotype as assessed by opsonophagocytosis
Description
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.
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.
Title
Tolerance of the double-dose compared to single dose of Prevenar®
Description
Presence of local and/or systemic reaction detailed on a questionary (fever, headache, fatigue, chills, rash, muscle pain, joint pain)
Time Frame
During the two weeks after both vaccines injection
Title
Clinical efficiency
Description
Pneumococcal documented infection during treatment (pneumonia, meningitis, acute media otitis, bacteremia) with proof of pneumococcal presence (on blood cultures, chest radiography, other samples)
Time Frame
During all the study (one year for each patient)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ZOHA MAAKAROUN-VERMESSE, MD-PHD
Phone
+33247478767
Email
Z.MAAKAROUN-VERMESSE@chu-tours.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas CHALOPIN
Email
tomchalopin@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ZOHA MAAKAROUN-VERMESSE, MD-PHD
Organizational Affiliation
University Hospital of TOURS
Official's Role
Study Director
Facility Information:
Facility Name
GYAN
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuel GYAN, MD-PhD
Email
e.gyan@chu-tours.fr

12. IPD Sharing Statement

Learn more about this trial

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

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