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

December 18, 2023 updated by: Fondazione Italiana Linfomi - ETS
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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy
        • Active, not recruiting
        • A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia
      • Ancona, Italy, 60126
      • Aviano, Italy
        • Recruiting
        • Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
        • Contact:
        • Principal Investigator:
          • Pietro Bulian, MD
      • Bari, Italy
        • Not yet recruiting
        • IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia
        • Contact:
        • Principal Investigator:
          • Attilio Guarini, MD
      • Bari, Italy
        • Active, not recruiting
        • AOU Policlinico Consorziale - U.O. Ematologia con Trapianto
      • Brescia, Italy
        • Not yet recruiting
        • ASST Spedali Civili di Brescia - Ematologia
        • Contact:
        • Principal Investigator:
          • Alessandro Re, MD
      • Cuneo, Italy, 12100
        • Active, not recruiting
        • A.O. S. Croce e Carle
      • Firenze, Italy, 50134
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi- Unità funzionale di ematologia
        • Principal Investigator:
          • Luca Nassi, MD
        • Contact:
      • Lecce, Italy
        • Not yet recruiting
        • Ospedale Vito Fazzi - Ematologia
        • Contact:
        • Principal Investigator:
          • Nicola Di Renzo, MD
      • Milano, Italy, 20132
        • Not yet recruiting
        • Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia
        • Contact:
          • Andres Ferreri, Dott.
        • Contact:
        • Principal Investigator:
          • Andres Ferreri, Dott.
      • Milano, Italy
        • Not yet recruiting
        • Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia
        • Contact:
        • Principal Investigator:
          • Francesca G Rossi, MD
      • Novara, Italy, 28100
        • Recruiting
        • AOU Maggiore della Carità di Novara - SCDU Ematologia
        • Principal Investigator:
          • Riccardo Moia, MD
        • Contact:
      • Padova, Italy, 35121
        • Active, not recruiting
        • AOU di Padova - Ematologia
      • Pavia, Italy
        • Not yet recruiting
        • IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
        • Principal Investigator:
          • Luca Arcaini, Prof.
        • Contact:
      • Piacenza, Italy, 29121
        • Not yet recruiting
        • Ospedale Guglielmo da Saliceto - U.O.Ematologia
        • Contact:
        • Principal Investigator:
          • Annalisa Arcari, MD
      • Reggio Emilia, Italy
        • Not yet recruiting
        • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia - Ematologia
        • Contact:
        • Principal Investigator:
          • Angelo Fama, MD
      • Rimini, Italy
        • Active, not recruiting
        • Ospedale degli Infermi di Rimini - U.O. di Ematologia
      • Roma, Italy
        • Not yet recruiting
        • Policlinico Umberto I - Universitа "La Sapienza" - Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
        • Contact:
        • Principal Investigator:
          • Alice Di Rocco, MD
      • Roma, Italy
        • Not yet recruiting
        • Universitа Cattolica S. Cuore - Ematologia
        • Contact:
        • Principal Investigator:
          • Stefan Hohaus, Prof.
      • Torino, Italy, 10126
        • Not yet recruiting
        • A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia
        • Contact:
        • Principal Investigator:
          • Carola Boccomini, MD
      • Torino, Italy
        • Not yet recruiting
        • A.O.U. Citta della Salute e della Scienza di Torino- Ematologia Universitaria
        • Principal Investigator:
          • Simone Ferrero, MD
        • Contact:
      • Trento, Italy
        • Not yet recruiting
        • Ospedale S. Chiara - S.S. di Ematologia
        • Contact:
        • Principal Investigator:
          • Chandrakala Toldo, MD
      • Treviso, Italy
        • Recruiting
        • Ospedale Ca' Foncello - S.C di Ematologia
        • Contact:
        • Principal Investigator:
          • Piero Maria Stefani, MD
      • Trieste, Italy
        • Active, not recruiting
        • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
      • Udine, Italy
        • Active, not recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica
      • Varese, Italy
        • Not yet recruiting
        • Ospedale di Circolo - U.O.C Ematologia
        • Principal Investigator:
          • Michele Merli, MD
        • Contact:
      • Verona, Italy, 37134
        • Recruiting
        • AOU Integrata di Verona - U.O. Ematologia
        • Contact:
        • Principal Investigator:
          • Francesca Maria Quaglia, MD
      • Vicenza, Italy
        • Not yet recruiting
        • ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
        • Principal Investigator:
          • Maria Chiara Tisi, MD
        • Contact:
    • MI
      • Milano, MI, Italy, 20162
        • Active, not recruiting
        • ASST Grande Ospedale Metropolitano Niguarda
    • PE
      • Pescara, PE, Italy, 65124
        • Not yet recruiting
        • P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
        • Contact:
        • Principal Investigator:
          • Elsa Pennese, MD
    • SI
      • Siena, SI, Italy, 53100
        • Recruiting
        • AOU Senese - U.O.C. Ematologia
        • Contact:
        • Principal Investigator:
          • Alberto Fabbri, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mutational analysis of Mantle Cell Lymphoma (MCL) driver genes
Time Frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
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)
Functional study of the B-Cell Receptor (BCR) activity by flow cytometry in Mantle Cell Lymphoma (MCL) cell samples
Time Frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
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)
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
Time Frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)

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)
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)
Time Frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
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)
To correlate results of biologic studies with clinical characteristics of patients
Time Frame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Italiana Linfomi - ETS

Investigators

  • Principal Investigator: Francesca Maria Quaglia, Azienda Ospedaliera Universitaria (AOU) Integrata di Verona - Unità Operativa di Ematologia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 8, 2023

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

December 1, 2023

Study Registration Dates

First Submitted

May 6, 2021

First Submitted That Met QC Criteria

May 6, 2021

First Posted (Actual)

May 12, 2021

Study Record Updates

Last Update Posted (Actual)

December 19, 2023

Last Update Submitted That Met QC Criteria

December 18, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIL_MANTLE-FIRST BIO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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