Lymphoma, Large B-Cell, Diffuse, Pneumococcal Infections
Conditions
Keywords
Lymphoma, pneumococcal vaccination, prime-boost, rituximab
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).
Interventions
BIOLOGICALAnti-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).
Sponsors
University Hospital, Tours
Hôpital Cochin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of responder patients at the 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Rates of responders patients to each serotype as assessed by opsonophagocytosis | - 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. |
| Tolerance of the double-dose compared to single dose of Prevenar® | 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) |
| Clinical efficiency | 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) |
Countries
France
Contacts
STUDY_DIRECTORZOHA MAAKAROUN-VERMESSE, MD-PHD
University Hospital of TOURS
Outcome results
None listed