An observational study in Follicular Lymphoma, sponsored by Fondazione Italiana Linfomi - ETS. Active, not recruiting at 14 sites in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-26.
Sponsored by Fondazione Italiana Linfomi - ETS · Observational
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.
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).
1,891 studies on the registry are indexed under Lymphoma, Follicular; 290 are open to participants now.
This study's enrollment of 56 is below the median of 150 across 195 observational studies indexed under Lymphoma, Follicular.
Browse Lymphoma, Follicular studies →Fondazione Italiana Linfomi - ETS is the lead sponsor of 91 studies on the registry; 23 are open to participants now.
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Patients affected by Follicular Lymphoma undergoing frontline induction immuno-chemotherapy and anti-CD20 maintenance within the prospective FIL_FOLL19 study
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
None
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patient affected by advanced Follicular Lymphoma undergoing front-line immunochemotherapy and antiCD-20 maintenance in the FIL\_FOLL19 trial
Diagnostic Test: Cellular immunity vs SARS-CoV-2 · Diagnostic Test: Humoral immunity vs SARS-CoV-2 · Diagnostic Test: Cellular immunity vs Varicella Zoster Virus · Diagnostic Test: Humoral immunity vs Varicella Zoster Virus · Diagnostic Test: Diphtheria toxin-binding IgG · Diagnostic Test: Tetanus toxoid-binding IgG · Diagnostic Test: T-cell populations and markers characterization
Evaluation of cellular immunity vs SARS-CoV-2 by ELISpot assay
Evaluation of Humoral immunity vs SARS-CoV-2 by ELISA assay (IgG anti-RBD and anti-N)
Evaluation of cellular immunity vs VZV by Enzyme-Linked immunoSPOT (ELISPOT) assay
Evaluation of humoral immunity vs VZV by ELISA (VZV gE-binding IgG)
Evaluation of diphtheria toxin-binding IgG by ELISA assay
Evaluation of tetanus toxoid-binding IgG by ELISA assay
Characterization of T-cell populations and markers by flow cytometry
Rate of patients with persistence of cell-mediated immunity induced by COVID-19 approved vaccines (at least three doses) after standard induction immuno-chemotherapy.
Proportion of patients with laboratory parameters of vaccine-induced cellular immunity against SARS-CoV-2 (by ELISpot assay) at EOI (after induction immuno-chemotherapy) vs proportion at baseline
Time frame: At the end of induction therapy (EOI) - About 8 months from treatment start
Rate of patients with persistence of cell-mediated immunity induced by COVID-19 approved vaccines (at least three doses) during anti-CD20 mAbs maintenance
Proportion of patients with laboratory parameters of vaccine-induced cellular immunity against SARS-CoV-2 (by ELISpot assay) during anti-CD20 maintenance (+12 months after EOI) vs proportion at baseline
Time frame: At +12 months of maintenance - About 20 months from treatment start
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.
Proportion of patients with laboratory parameters of vaccine-induced humoral immunity against SARS-CoV-2 (by ELISA assay detecting anti-receptor binding domain \[RBD\] and anti-nucleocapsid \[N\] IgG antibodies) after standard induction immuno-chemotherapy (EOI) and during anti-CD20 maintenance (+12 months after EOI) vs proportion at baseline (excluding patients who received pre-exposure tixagevimab/cilgavimab or other monoclonal antibodies).
Time frame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
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
Proportion of patients with laboratory parameters of vaccine-induced humoral (by ELISA assay detecting anti-glycoprotein E IgG antibodies) and/or cellular immunity (by ELISpot assay) against VZV at EOI and during anti-CD20 maintenance (+12 months after EOI) vs proportion at first detection after vaccination (in the subgroup of patients with a detectable serologic response at study entry).
Time frame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
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
Proportion of patients with laboratory parameters of vaccine-induced humoral immunity against diphtheria and tetanus (by ELISA assay detecting diphtheria toxin-binding IgG and tetanus toxoid-binding IgG) at EOI and during anti-CD20 maintenance (+12 months after EOI) vs proportion at baseline (in the subgroup of patients with a detectable serologic response at study entry).
Time frame: At the end of induction therapy (EOI) and at +12 months of maintenance - About 8 months and 20 months from treatment start respectively
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
Incidence of COVID-19 infections and their severity in vaccinated patients undergoing induction immuno-chemotherapy and maintenance and correlation with the level of immunity as measured by humoral and/or cellular immune parameters at the time point before the event as well as with eventual tixagevimab/cilgavimab administration (or prophylaxis with other monoclonal antibodies) and with dominant SARS-CoV-2 variant/subvariant at the time of infection
Time frame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
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
Incidence of zoster infections and their severity in vaccinated patients undergoing induction immuno-chemotherapy and maintenance and correlation with the level of immunity as measured by humoral and/or cellular immune parameters at the time point before the event.
Time frame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
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
Description in the study population at study entry and at the latest timepoint of the percentage and absolute number of T lymphocytes populations and their subset distribution, expression of markers of activation and of functional exhaustion and immune checkpoints on T lymphocytes and T helper (Th) polarization of the CD4+ T-cell population by flow cytometry
Time frame: From baseline (before therapy) up to 20 months from treatment start (+12 months of maintenance)
This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Fondazione Italiana Linfomi - ETS