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

Pneumococcal Infections Clinical Trial

— EVAPOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04214444
• Other study ID #: DR190111-EVAPOR
• Secondary ID: 2019-002542-20
• Status: Recruiting
• Phase: Phase 3
• Start date: July 3, 2020
• Est. completion date: July 3, 2022

Study information

• Verified date: May 2021
• Source: University Hospital, Tours
• Contact: ZOHA MAAKAROUN-VERMESSE, MD-PHD
• Phone: +33247478767
• Email: Z.MAAKAROUN-VERMESSE[@]chu-tours.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: July 3, 2022
• Est. primary completion date: July 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Pneumococcal Infections

Intervention

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).

Locations

Country	Name	City	State
France	GYAN	Tours

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Tours	Hôpital Cochin

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	- 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	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.	- 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	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)	During the two weeks after both vaccines injection
Secondary	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)	During all the study (one year for each patient)