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

Regional University Hospital Center (CHRU)

Status and phase: Unknown; Phase 3

Conditions: Lymphoma, Large B-Cell, Diffuse; Pneumococcal Infections

Treatments: Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma

Study type: Interventional

Funder types: Other

Identifiers

NCT04214444

DR190111-EVAPOR

2019-002542-20 (EudraCT Number)

Details and patient eligibility

About

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%).

Full 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).

Enrollment: 36 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

Single-dose before treatment

Active Comparator group

Description:

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

Treatment:

Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma

Single-dose after treatment

Active Comparator group

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

Treatment:

Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma

Double-dose before treatment

Experimental group

Description:

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

Treatment:

Biological: Anti-pneumococcal vaccination with prime-boost strategy in patients with diffuse large B cell lymphoma