Infections

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Communicable Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Pneumococcal Infections

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Streptococcal Infections

Bacterial Infections

Gram-Positive Bacterial Infections

Mycoses

Bacterial Infections and Mycoses

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Heptavalent Pneumococcal Conjugate Vaccine

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.

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).

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

ZOHA MAAKAROUN-VERMESSE, MD-PHD

Thomas CHALOPIN

Emmanuel GYAN, MD-PhD

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%).

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).

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

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

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.

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.

Presence of local and/or systemic reaction detailed on a questionary (fever, headache, fatigue, chills, rash, muscle pain, joint pain)

Pneumococcal documented infection during treatment (pneumonia, meningitis, acute media otitis, bacteremia) with proof of pneumococcal presence (on blood cultures, chest radiography, other samples)

Hôpital Cochin

University Hospital, Tours

Recurrence

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Vaccine-Preventable Diseases

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Vaccines

Immunologic Factors

Patients receive one dose of Prevenar13 followed by one dose of Pneumovax23 2 months later

Prevnar13

Hannah Garcia Garrido, MD

Koen de Heer, MD

In this study the antibody response after vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine (PPSV23) in adults with chronic lymphocytic leukemia will be investigated.

Background Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of both invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal vaccination for all CLL patients, preferably before initiation of treatment. The recommended vaccination schedule consists of Prevenar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23, a 23-valent polysaccharide vaccine (PPSV23).

The immunological efficacy of this sequential vaccination schedule in CLL patients is unknown. Previous studies have only investigated responses to either PCV13 or PPSV23 alone. Responses to PPSV23 alone are poor in CLL patients. Responses to the 7-valent pneumococcal conjugated vaccine (PCV7) or PCV13 are higher compared to responses to PPSV23, but lower compared to responses in healthy individuals. More advanced disease stage and lower baseline IgG negatively influence responses to vaccination.

The aim of this observational cohort study is to assess the immunogenicity of the currently recommended vaccination schedule of PCV13 followed by PPSV23 in CLL patients.

2. Methods Study design and population As part of routine care, all adult CLL patients naïve to pneumococcal vaccination and cared for in the Amsterdam UMC-location AMC, Flevoziekenhuis, HagaZiekenhuis, Elisabeth-TweeSteden Hospital, Noordwest Ziekenhuisgroep, Albert Schweitzer Hospital and Ikazia Hospital receive one dose of Prevenar13® followed by one dose of Pneumovax23® 2 months later. According to the current local standard of care for immunosuppressed individuals, the response to vaccination will be assessed by measuring pneumococcal antibody levels before and 4-8 weeks after vaccination.

After obtaining informed consent clinical data will be collected by a trained medical student, nurse or research assistant according to a standardized electronic case report form (Castor EDC). Variables included in the case report form are: age, sex, smoking behaviour, Rai stage (I/II/III), past or ongoing chemotherapy, ongoing steroid treatment, past or ongoing therapy with a monoclonal anti-CD20 antibody (and date of last infusion), baseline total IgG level, baseline lymphocyte count, baseline haemoglobin level, baseline platelet level, baseline pneumococcal IgG levels, post-vaccination pneumococcal IgG levels, date of PCV and PPSV23 vaccine administration, date of antibody measurements, comorbidities (Charlson comorbitiy index).

Laboratory methods and definitions Serotype-specific pneumococcal immunoglobulin G (IgG) concentrations to 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F) and 4 serotypes unique to PPSV23 (8, 15B, 20, 33F) will be determined in the immunology laboratory of the UMC Utrecht. A validated multiplex immunoassay will be used (Luminex® technology). Serologic response will be defined as a ≥4-fold increase in serotype specific anti-pneumococcal IgG for ≥70% of measured. Serologic protection will be defined as an antibody concentration ≥1.3 mcg/ml for ≥70% of all measured serotypes, according to the definition of the American Academy of Allergy, Asthma \& Immunology. In addition, because most previous studies used the WHO cut-off for protection in infants (≥0.35mcg/ml) data will also be analyzed by the infant correlate of protection to be able to compare the results with previous studies.

Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia

Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Chronic Lymphocytic Leukaemia.

Proportion of participants with a ≥4-fold increase in serotype specific anti-pneumococcal IgG for ≥6/9 serotypes

Antibody concentration ≥1.3 mcg/ml for ≥6/9 serotypes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab	NCT04214444	Pneumococcal In... Lymphoma, Large...	Anti-pneumococc...	18 Years - 80 Years	University Hospital, Tours
Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia	NCT05145101	Pneumococcal In... Chronic Lymphoc... Vaccine-Prevent... Invasive Pneumo...	Prevnar13	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia	NCT05145101	Pneumococcal In... Chronic Lymphoc... Vaccine-Prevent... Invasive Pneumo...	Prevnar13	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Evaluation of Prime-boost Anti-pneumococcal Vaccination in Patients With Diffuse Large B Cell Lymphoma Treated With Rituximab	NCT04214444	Pneumococcal In... Lymphoma, Large...	Anti-pneumococc...	18 Years - 80 Years	University Hospital, Tours
Pneumococcal Vaccination in Patients With Chronic Lymphocytic Leukaemia	NCT05145101	Pneumococcal In... Chronic Lymphoc... Vaccine-Prevent... Invasive Pneumo...	Prevnar13	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Spots Global Cancer Trial Database for pneumococcal infections