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

NCT ID: NCT04882475

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 160 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-08
• Study Completion Date: 2026-04-30

Brief 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.

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.

Conditions

Mantle Cell Lymphoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

MCL patients relapsed or refractory to rituximab and induction chemotherapy with curative intent

An 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).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesca Maria Quaglia

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria (AOU) Integrata di Verona - Unità Operativa di Ematologia

Locations

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, Italy

AOU Senese - U.O.C. Ematologia

Siena, SI, Italy

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

Aviano, , Italy

ASST Spedali Civili di Brescia - Ematologia

Brescia, , Italy

A.O. S. Croce e Carle

Cuneo, , Italy

Azienda Ospedaliera Universitaria Careggi- Unità funzionale di ematologia

Florence, , Italy

AOU Maggiore della Carità di Novara - SCDU Ematologia

Novara, , Italy

AOU di Padova - Ematologia

Padua, , Italy

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, , Italy

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

Reggio Emilia, , Italy

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

Torino, , Italy

Ospedale Ca' Foncello - S.C di Ematologia

Treviso, , Italy

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Trieste, , Italy

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

Udine, , Italy

AOU Integrata di Verona - U.O. Ematologia

Verona, , Italy

ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

Vicenza, , Italy

Countries

Italy

Other Identifiers

FIL_MANTLE-FIRST BIO

Identifier Type: -

Identifier Source: org_study_id