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Mantle Cell LymphomaNCT04882475

Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.

An observational study of Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 16 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Retrospective observational study with a prospective biological evaluation of an historical cohort of first relapsed-refractory patients with mantle cell lymphoma who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Mantle Cell Lymphoma
How many people
160 participants
Where
16 sitesItaly
Study dates
8 Feb 2023to Apr 2026
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with Mantle Cell Lymphoma (MCL) who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent.

Who may be able to join

  • Patients with histologically documented diagnosis of Mantle Cell Lymphoma (MCL) as defined in the 2016 edition of the World Health Organization (WHO) classification, with available tissue for revision and additional studies;
  • Diagnosis of Mantle Cell Lymphoma (MCL) between 1st of January 2008 and 30th of June 2020;
  • Adults, 18-80 years at diagnosis;
  • Relapsed or refractory disease after rituximab and chemotherapy containing induction regimens with curative intent.
  • Treatment at relapse or progression on an intention-to-treat basis (ITT): at least one cycle of Chemo-immunotherapy (CIT), Bruton Tyrosine kinase inhibitors (BTKi), or alternative drugs combination;
  • Subject understanding and voluntarily signing an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any study-specific procedures.

Who cannot join

  • Unavailability of the samples requested by the study;
  • Any histology other than Mantle Cell Lymphoma (MCL);
  • Patients treated with front line regimens containing only rituximab or with palliative therapy;
  • Untreated patients; patients undergoing watchful waiting approach.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Italy16 sites

  • Centro Riferimento Oncologico - S.O.C. Oncologia Medica A

    Aviano

  • ASST Spedali Civili di Brescia - Ematologia

    Brescia

  • A.O. S. Croce e Carle

    Cuneo, 12100

  • Azienda Ospedaliera Universitaria Careggi- Unità funzionale di ematologia

    Florence, 50134

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, MI, 20162

  • AOU Maggiore della Carità di Novara - SCDU Ematologia

    Novara, 28100

  • AOU di Padova - Ematologia

    Padova, 35121

  • Ospedale Guglielmo da Saliceto - U.O.Ematologia

    Piacenza, 29121

  • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia - Ematologia

    Reggio Emilia

  • AOU Senese - U.O.C. Ematologia

    Siena, SI, 53100

  • A.O.U. Citta della Salute e della Scienza di Torino- Ematologia Universitaria

    Torino

  • Ospedale Ca' Foncello - S.C di Ematologia

    Treviso

  • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

    Trieste

  • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica

    Udine

  • AOU Integrata di Verona - U.O. Ematologia

    Verona, 37134

  • ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

    Vicenza

Other trials in Italy

About this study

Retrospective observational study with a prospective biological evaluation of an historical cohort of first relapsed-refractory patients with mantle cell lymphoma who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent.

Read the detailed description

Biological samples from 80 Mantle Cell Lymphoma (MCL) patients will be collected and analyzed in 30 Italian sites in 36 months.

Patients will be identified and selected both on a clinical base and according to the availability of Formaline-fixed paraffin-embedded (FFPE) material, frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. They will be analyzed in 4 subgroups, each with different clinical specificity: 1) refractory to Induction Chemoimmunotherapy (CIT); 2) refractory to Bruton Tyrosine kinase (BTK) inhibitors (BTKi); 3) sensitive to induction Induction Chemoimmunotherapy (CIT); 4) sensitive to BTK inhibitors (BTKi).

Each group will undergo central pathology revision with other immunohistochemical studies (Verona, Dr. Parisi; Milano, Prof. Ponzoni; Vicenza, Dr. D'Amore; Brescia, Prof. Facchetti). Formaline-fixed paraffin-embedded (FFPE) diagnostic specimens of Mantle Cell Lymphoma (MCL) will be screened by immunohistochemistry for the expression of immunoglobulin (Ig) heavy chains to identify Mantle Cell Lymphoma (MCL) cases lacking Immunoglobulin (Ig) expression.

Cytofluorimetric and molecular studies will be performed in the laboratories of the Verona University and at IFOM (Istituto FIRC di Oncologia Molecolare (FIRC = Fondazione Italiana per la Ricerca sul Cancro)). Specific methods will be used: Flow cytometry for the status of surface Ig expression and multiplexed phospho-specific flow cytometry, NGS (Next Generation Sequencing), Immunoglobulin (IgH/IgL V(D)J) profiling by BIOMED2 protocol-based, NGS (Next Generation Sequencing) technology in the relapsed-refractory mantle cell lymphoma (R/R MCL) cases, Chromatin accessibility studies by Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) (on viable cell suspensions or frozen pellets) and Gene Expression Profiling (GEP) by RNA-sequencing and RNA studies of the MALT1-MYC ((Mucosa-associated lymphoid tissue lymphoma translocation protein 1 - MYC) pathway.

Keywords
MCL (Mantle Cell Lymphoma), first relapsed-refractory patients, Histopathological characterization, Flow cytometry, NGS (Next Generation Sequencing), Gene Expression Profiling, RNA, BTKi (Bruton Tyrosine kinase inhibitors), Retrospective observational study, DNA
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04882475
Study groupRoleWhat they receive
MCL patients relapsed or refractory to rituximab and induction chemotherapy with curative intentAn historical cohort of patients will be identified and selected both on a clinical base and according to the availability of Formaline-fixed paraffin-embedded (FFPE) material, frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. Samples will be analyzed in 4 subgroups, each with different clinical specificity: 1. refractory to Induction Chemoimmunotherapy (CIT); 2. refractory to Bruton Tyrosine kinase (BTK) inhibitors (BTKi); 3. sensitive to Induction Chemoimmunotherapy (CIT); 4. sensitive to Bruton Tyrosine kinase (BTK) inhibitors (BTKi).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Histopathological characterization of patients with Mantle Cell Lymphoma (MCL)

    Histopathological characterization of patients with mantle cell lymphoma (MCL) who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent. 80 Mantel Cell Lymphoma (MCL) patients stratified according to Chemo-immunotherapy (CIT) or Bruton Tyrosine kinase inhibitors (BTKi) resistance (20 for each of the groups previously identified) will undergo central pathology revision with assessment of Immunoglobulin (Ig) expression and other histopathological studies.

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

Secondary outcomes (5)

  1. Mutational analysis of Mantle Cell Lymphoma (MCL) driver genes

    Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform a mutational analysis for Mantle Cell Lymphoma (MCL) driver genes: Next Generation Sequencing (NGS) on approximately 80 cases of Mantle Cell Lymphoma (MCL), including 20 cases Relapsed/Refractory (R/R) to Bruton Tyrosine kinase inhibitors (BTKi)

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

  2. Functional study of the B-Cell Receptor (BCR) activity by flow cytometry in Mantle Cell Lymphoma (MCL) cell samples

    Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform a functional study of the B-Cell Receptor (BCR) activity: multiplexed phospho-specific flow cytometry on 10-20 Relapsed/Refractory (R/R) Mantle Cell Lymphoma cases.

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

  3. To understand the mechanisms of evasion from B-Cell Receptor (BCR) requirement, with particular focus on Mantle Cell Lymphoma (MCL) cases that are resistant to Chemo-immunotherapy (CIT) and/or Bruton Tyrosine kinase (BTK) inhibition

    Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to understand the mechanisms of evasion from B-Cell Receptor (BCR) requirement as follow:

    • Immunoglobulin (IgH/IgL V(D)J) profiling by Next Generation Sequencing (NGS) on 80 mantle cell lymphoma (MCL) cases;
    • Chromatin accessibility studies (Assay for Transposase-Accessible Chromatin sequencing, ATAC-seq) on approximately 20 cases among the Immunoglobulin (Ig)-negative identified cases or Bruton Tyrosine kinase inhibitors (BTKi) refractory cases, irrespective of their B-Cell Receptor (BCR) status, and on other 20 cases, from the group of patients sensitive to Bruton Tyrosine kinase inhibitors (BTKi);
    • Gene Expression Profiling (GEP) by RNA-seq, on about 20 cases selected on the basis of results of the Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) analysis;

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

  4. Unveil the role of the MALT1-MYC (Mucosa-associated lymphoid tissue lymphoma translocation protein 1 - MYC) pathway in Mantle Cell Lymphoma (MCL) cases expressing or not the BCR (B-Cell Receptor)

    Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform RNA studies on 20 cases

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

  5. To correlate results of biologic studies with clinical characteristics of patients

    About 80 cases of Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) with available tissue samples will be considered for correlation between biological studies with clinical characteristics of patients, response to treatment and conventional outcomes (Progression Free Survival, Progression Free Survival at 2 years, Overall Survival, Overall Survival at 2 years)

    Measured: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2021
  2. Study start8 Feb 2023
  3. Primary completionApr 2026 (estimated)
  4. Study completionApr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04882475
Sponsor's protocol ID
FIL_MANTLE-FIRST BIO
Status last verified
Dec 2025
First submitted
6 May 2021
Last updated
5 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

An observational study of Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 16 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Histopathological characterization of patients with Mantle Cell Lymphoma (MCL) (time frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04882475.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2026.

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