Clinical trial NCT04882475: Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.
Official title: Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2021-05-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Histopathological characterization of patients with Mantle Cell Lymphoma (MCL)
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Secondary outcomes:
measure: Mutational analysis of Mantle Cell Lymphoma (MCL) driver genes
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: Functional study of the B-Cell Receptor (BCR) activity by flow cytometry in Mantle Cell Lymphoma (MCL) cell samples
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: 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
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: 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)
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
measure: To correlate results of biologic studies with clinical characteristics of patients
timeFrame: The endpoint will be evaluated from the beginning to the end of the study (up to 36 months)
Other outcomes:
Locations:
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: MI
city: Pescara
country: Italy
facility: P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
state: PE
city: Siena
country: Italy
facility: AOU Senese - U.O.C. Ematologia
state: SI
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo, SC Ematologia
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti - Clinica di Ematologia
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
city: Bari
country: Italy
facility: AOU Policlinico Consorziale - U.O. Ematologia con Trapianto
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia - Ematologia
city: Cuneo
country: Italy
facility: A.O. S. Croce e Carle
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi- Unità funzionale di ematologia
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi - Ematologia
city: Milano
country: Italy
facility: Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda - Ematologia
city: Novara
country: Italy
facility: AOU Maggiore della Carità di Novara - SCDU Ematologia
city: Padova
country: Italy
facility: AOU di Padova - Ematologia
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - U.O.Ematologia
city: Reggio Emilia
country: Italy
facility: Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia - Ematologia
city: Rimini
country: Italy
facility: Ospedale degli Infermi di Rimini - U.O. di Ematologia
city: Roma
country: Italy
facility: Policlinico Umberto I - Universitа "La Sapienza" - Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
city: Roma
country: Italy
facility: Universitа Cattolica S. Cuore - Ematologia
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino- Ematologia Universitaria
city: Trento
country: Italy
facility: Ospedale S. Chiara - S.S. di Ematologia
city: Treviso
country: Italy
facility: Ospedale Ca' Foncello - S.C di Ematologia
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica
city: Varese
country: Italy
facility: Ospedale di Circolo - U.O.C Ematologia
city: Verona
country: Italy
facility: AOU Integrata di Verona - U.O. Ematologia
city: Vicenza
country: Italy
facility: ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
Study officials:
affiliation: Azienda Ospedaliera Universitaria (AOU) Integrata di Verona - Unità Operativa di Ematologia
name: Francesca Maria Quaglia
role: PRINCIPAL_INVESTIGATOR
References: