Clinical trial NCT04214444: Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pneumococcal Infections
Lymphoma, Large B-Cell, Diffuse
Keywords: Lymphoma
pneumococcal vaccination
prime-boost
rituximab
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: Hôpital Cochin
First posted: 2020-01-02
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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).

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

Primary outcomes:
measure: Proportion of responder patients at the end of treatment.
timeFrame: - 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 outcomes:
measure: Rates of responders patients to each serotype as assessed by opsonophagocytosis
timeFrame: - 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.
measure: Tolerance of the double-dose compared to single dose of Prevenar®
timeFrame: During the two weeks after both vaccines injection
measure: Clinical efficiency
timeFrame: During all the study (one year for each patient)
Other outcomes:
Locations:
city: Tours
country: France
facility: GYAN
Study officials:
affiliation: University Hospital of TOURS
name: ZOHA MAAKAROUN-VERMESSE, MD-PHD
role: STUDY_DIRECTOR
References: