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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04882475
Other study ID # FIL_MANTLE-FIRST BIO
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date February 8, 2023
Est. completion date December 2023

Study information

Verified date December 2023
Source Fondazione Italiana Linfomi - ETS
Contact Marina Cesaretti
Phone 0039 059 9769913
Email mcesaretti@filinf.it
Is FDA regulated No
Health authority
Study type Observational

Clinical 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 80
Est. completion date December 2023
Est. primary completion date December 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Italy A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia Alessandria
Italy AOU Ospedali Riuniti - Clinica di Ematologia Ancona
Italy Centro Riferimento Oncologico - S.O.C. Oncologia Medica A Aviano
Italy AOU Policlinico Consorziale - U.O. Ematologia con Trapianto Bari
Italy IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia Bari
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 Firenze
Italy Ospedale Vito Fazzi - Ematologia Lecce
Italy ASST Grande Ospedale Metropolitano Niguarda Milano MI
Italy Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia Milano
Italy Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia Milano
Italy AOU Maggiore della Carità di Novara - SCDU Ematologia Novara
Italy AOU di Padova - Ematologia Padova
Italy IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia Pavia
Italy P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi Pescara PE
Italy Ospedale Guglielmo da Saliceto - U.O.Ematologia Piacenza
Italy Azienda Unit? Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia - Ematologia Reggio Emilia
Italy Ospedale degli Infermi di Rimini - U.O. di Ematologia Rimini
Italy Policlinico Umberto I - Universit? "La Sapienza" - Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione Roma
Italy Universit? Cattolica S. Cuore - Ematologia Roma
Italy AOU Senese - U.O.C. Ematologia Siena SI
Italy A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia Torino
Italy A.O.U. Citta della Salute e della Scienza di Torino- Ematologia Universitaria Torino
Italy Ospedale S. Chiara - S.S. di Ematologia Trento
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 Ospedale di Circolo - U.O.C Ematologia Varese
Italy AOU Integrata di Verona - U.O. Ematologia Verona
Italy ULSS 8 Berica - Ospedale S. Bortolo - Ematologia Vicenza

Sponsors (1)

Lead Sponsor Collaborator
Fondazione Italiana Linfomi - ETS

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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) The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary 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. The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary 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;
The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary 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 The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary 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) The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
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