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

NCT04882475 | Active Not Recruiting

• 1 other identifier: FIL_MANTLE-FIRST BIO
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 16

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.

Conditions

Mantle Cell Lymphoma

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

• Mutational analysis of Mantle Cell Lymphoma (MCL) driver genes

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

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

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

• 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

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

• 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)

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

• To correlate results of biologic studies with clinical characteristics of patients

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

Study Arms (1)

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).

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (16)

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

Location

AOU Senese - U.O.C. Ematologia

Siena, SI, 53100, Italy

Location

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

Aviano, Italy

Location

ASST Spedali Civili di Brescia - Ematologia

Brescia, Italy

Location

A.O. S. Croce e Carle

Cuneo, 12100, Italy

Location

Azienda Ospedaliera Universitaria Careggi- Unità funzionale di ematologia

Florence, 50134, Italy

Location

AOU Maggiore della Carità di Novara - SCDU Ematologia

Novara, 28100, Italy

Location

AOU di Padova - Ematologia

Padua, 35121, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, 29121, Italy

Location

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

Reggio Emilia, Italy

Location

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

Torino, Italy

Location

Ospedale Ca' Foncello - S.C di Ematologia

Treviso, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Trieste, Italy

Location

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

Udine, Italy

Location

AOU Integrata di Verona - U.O. Ematologia

Verona, 37134, Italy

Location

ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

Vicenza, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

For the primary objective of the study: Formaline-fixed paraffin-embedded (FFPE) material. For the secondary objectives of the study: viable cell suspensions, DNA extracted from Formaline-fixed paraffin-embedded (FFPE) tissue sections or frozen pellets, frozen cell suspensions.

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francesca Maria Quaglia

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 12, 2021
• Study Start: February 8, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

IT (16)