Clinical trial NCT06070961: Prospective Biological Study to Evaluate the Persistence of COVID-19 Vaccine and Other Vaccines'-Induced Immune Responses in Follicular Lymphoma Patients Undergoing Frontline Induction Immuno-chemotherapy and Anti-CD20 Maintenance
Official title: Prospective Biological Study to Evaluate the Persistence of COVID-19 Vaccine and Other Vaccines'-Induced Immune Responses in Follicular Lymphoma Patients Undergoing Frontline Induction Immuno-chemotherapy and Anti-CD20 Maintenance
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Follicular Lymphoma
Keywords: Lymphoma
Follicular
Immunochemotherapy
FL
Vaccine
COVID19
SARS-COV-2
Tetanus
Zoster
VZV
Rituximab
obinotuzumab
FOLL19
FIL_FOLL19
diphtheria
Maintenance
Humoral
Cellular
Immunity
Induction
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2023-10-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients affected by Follicular Lymphoma undergoing frontline induction immuno-chemotherapy and anti-CD20 maintenance within the prospective FIL_FOLL19 study

Brief summary: This is a prospective biological study evaluating the persistence of COVID-19 vaccine and other vaccines' (zoster, diphtheria and tetanus)-induced immunity in a subgroup patient affected by Follicular Lymphoma requiring treatment undergoing frontline induction immuno-chemotherapy and anti-CD20 maintenance within the prospective FIL_FOLL19 study (NCT05058404).

Blood samples from patients will be collected before and at planned timepoints during treatment to evaluate humoral and cellular immunity against SARS-COV-2, VZV, tetanus and diphtheria and T-cell markers characterization.

Detailed description: Patients (pts) with follicular lymphoma (FL) were reported to be at high risk for hospitalization and death from COVID-19 infection, especially if exposed to anti-CD20 monoclonal antibodies (mAbs)-based therapy. A large amount of studies unequivocally demonstrated that anti-CD20 mAbs-containing therapies typically impair the development of protective levels of neutralizing anti-spike antibodies after immunization with full course of approved mRNA-based COVID-19 vaccines (up to 12 months after last anti-CD20 infusion). Moreover, booster doses seem to induce seroconversion only in a minority of such pts. On the contrary, preliminary findings seem to suggest that a substantial proportion of vaccinated pts with B-cell lymphoma (B-NHL) mount detectable SARS-CoV-2-specific T-cell responses (as measured by assays evaluating IFN-Y secretion after stimulation with SARS-CoV-2 peptides), independently from humoral response status.

For newly diagnosed FL pts current guidelines suggest to complete the vaccination with booster dose(s) before treatment initiation, as anti-CD20 mAbs seems to spare pre-established humoral immunity to COVID-19 vaccine, although data supporting this finding are scanty.5 Furthermore, data about long term persistence of pre-established cellular immunity in this setting are lacking, although preliminary findings in unselected immunosuppressed pts suggest that it decline over time without significant difference with respect to the general population.

The novel adjuvanted recombinant zoster vaccine demonstrated lower humoral immune response in pts with B-NHL with respect to other pts, probably due to anti-CD20 therapy, while cellular immunity was not affected, although the small number of pts requires further investigation.

Very few data concerning persistence of immunity to childhood vaccines after anti-CD20-based therapy are available and suggest that humoral immunity to diphtheria and tetanus may be significantly impaired after therapy.

This is a prospective biological study evaluating the persistence of COVID-19 vaccine and other vaccines' (zoster, diphtheria and tetanus)-induced immunity in a subgroup of FL patients undergoing frontline induction immuno-chemotherapy and anti-CD20 maintenance within the prospective FIL_FOLL19 study (NCT05058404).

After the signature of a specific informed consent, eligible patients will receive a questionnaire evaluating vaccination history, past infection history and treatment, and passive immune prophylaxis (e.g. tixagevimab/cilgavimab administration). A baseline blood sample will be collected before the initiation of treatment and will be sent to the central laboratory, where specific analyses evaluating vaccine-induced cellular and/or humoral immunity against COVID-19, VZV, diphtheria and tetanus will be performed.

COVID-19 cellular and humoral immunity will be evaluated in all patients at all available timepoints.

Humoral and cellular immunity for VZV will be evaluated for all patients at study entry. In the subgroup of patients with a detectable serologic response at study entry, humoral and cellular immunity will be also evaluated at all available later timepoints.

Humoral immunity for diphtheria and tetanus will be evaluated for all patients at study entry. In the subgroup of patients with a detectable serologic response at study entry, humoral immunity will be also evaluated at all available later timepoints.

T-cell immunological parameters will be evaluated at study entry and 12 months after EOI (or early withdrawal).

Eligibility criteria: Inclusion Criteria:

1. Enrolment in FIL_FOLL19 study
2. Previous vaccination for COVID-19 (at least 3 doses)
3. Availability of informations about COVID-19 and other vaccines previously administered (vaccination records)
4. Willingness to comply with blood collection timepoints required for vaccination immunity evaluation
5. Signature of specific informed consent form

Exclusion Criteria:

None

Primary outcomes:
measure: Rate of patients with persistence of cell-mediated immunity induced by COVID-19 approved vaccines (at least three doses) after standard induction immuno-chemotherapy.
timeFrame: At the end of induction therapy (EOI) - About 8 months from treatment start
Secondary outcomes:
measure: Rate of patients with persistence of cell-mediated immunity induced by COVID-19 approved vaccines (at least three doses) during anti-CD20 mAbs maintenance
timeFrame: At +12 months of maintenance - About 20 months from treatment start
measure: Rate of patients with persistence of humoral immunity induced by COVID-19 approved vaccines (at least three doses) after standard induction immuno-chemotherapy and during maintenance.
timeFrame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
measure: Rate of patients (with a detectable serologic response at study entry) with persistence of humoral and cellular immunity induced by adjuvanted recombinant zoster vaccine after standard induction immuno-chemotherapy and during maintenance
timeFrame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
measure: Rate of patients (with a detectable serologic response at study entry) with persistence of humoral immunity induced by childhood vaccines (diphtheria and tetanus) after standard induction immuno-chemotherapy and during maintenance
timeFrame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
measure: Rate of COVID-19 infection events and severity in vaccinated patients and correlation with humoral and/or cellular immunity with eventual tixagevimab/cilgavimab or other MAb prophylaxis and with dominant SARS-CoV-2 variant/subvariant at time of infection
timeFrame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
measure: Rate of zoster infection events and their severity in vaccinated patients and correlation with the level of immunity as measured by humoral and/or cellular immune parameters at the time point before the event
timeFrame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
measure: Characterization of multiple T-cell immunological parameters before and after standard induction immuno-chemotherapy in patients with follicular lymphoma treated within the prospective FIL_FOLL19 study
timeFrame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia
state: IT
city: Biella
country: Italy
facility: Nuovo Ospedale degli Infermi, SSD Ematologia
state: IT
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
state: IT
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico Fondazione IRCCS Ca' Granda - Ematologia
state: IT
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità di Novara - S.C.D.U. Ematologia
state: IT
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo - Divisione di Ematologia
state: IT
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - U.O. Ematologia
state: IT
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia U
state: IT
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - S.C. Ematologia
state: IT
city: Varese
country: Italy
facility: Ospedale di Circolo - U.O.C. Ematologia
state: IT
city: Brescia
country: Italy
facility: ASST Spedali Civili - S.C. Ematologia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
city: Siena
country: Italy
facility: A.O.U. Senese - U.O.C. Ematologia
Study officials:
affiliation: U.O.C Ematologia, Ospedale di Circolo, Varese
name: Michele Merli, MD
role: PRINCIPAL_INVESTIGATOR
References: