Non Hodgkin LymphomaBCL6-RINHLNCT06424379
BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.
An observational study of Non Hodgkin Lymphoma and Follicular Lymphoma, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most… Read more about this study
- Who is it for?
- Ages 25 to 100 years
- Conditions the study is for
- Non Hodgkin Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
- What is being tested?
- Histopathological analysis and Molecular analysis
- How many people
- 135 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2024to 30 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients diagnosed with non-Hodgkin lymphoma from the routine diagnostic archives of the pathology department of CHU Lyon Sud between January 2016 and August 2023 and with BCL6-R detected by FISH analysis will be included in the study. A cohort of 135 cases will be assembled and subjected to the analysis. This dataset will be reviewed by two haematopathologists to ensure the inclusion of the most relevant cases. Selection will favor cases with substantial histological material and available clinical, immunophenotypic and cytogenetic data. Comparative assessments will be conducted between distinct subtypes of NHL exhibiting BCL6-R, including FLs, MZLs, and DLBCLs.
Who may be able to join
- Diagnostic of non-Hodgkin's lymphoma at anatomy and cytology department of Lyon Sud hospital
- Rearrangement of the BCL6 gene detected by FISH analysis
- Diagnostic of the disease between january 2016 and december 2023
Who cannot join
- Patients diagnosed with primary cutaneous centrofollicular B lymphoma, composite lymphoma, anaplastic B lymphoma or primary B lymphoma of the mediastinum.
- Presence of a rearrangement of the BLC2 gene or the CMYC gene in FISH
- Presence of a non-significant BCL6 gene rearrangement (<5% of rearranged cells)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Clinical, Histological, Immunohistochemical and Molecular Impact of BCL6 Gene Rearrangement in Most Prevalent Non-Hodgkin Lymphomas
Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.
Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.
Read more
A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.
FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.
MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.
Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.
- Conditions
- Non Hodgkin Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Diffuse Large B Cell Lymphoma
- Being tested
- Histopathological analysis, Molecular analysis
- Keywords
- Non Hodgkin Lymphoma, BCL6 gene rearrangement, Next generation sequencing
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Histopathological analysisOther
Morphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud.
A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm.
Molecular analysisGenetic
Next-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels.
RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL).
| Study group | Role | What they receive |
|---|---|---|
| Follicular lymphomas with BCL6 gene rearrangement | Diagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. Receives: Other: Histopathological analysis; Genetic: Molecular analysis | |
| Marginal zone lymphomas with BCL6 gene rearrangement | Diagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. Receives: Other: Histopathological analysis; Genetic: Molecular analysis | |
| Diffuse large B-cells lymphomas with BCL6 gene rearrangement | Diagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. Receives: Other: Histopathological analysis; Genetic: Molecular analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of LF and MZL with BCL6-R.
An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.
Measured: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Comparison of LF and MZL with BCL6-R.
Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.
Measured: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2024
- Study start1 Jan 2024
- Primary completion1 Jun 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424379
- Sponsor's protocol ID
- 69HCL24_0515
- Acronym
- BCL6-RINHL
- Status last verified
- May 2024
- First submitted
- 16 May 2024
- Last updated
- 23 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Clinical, Histological, Immunohistochemical and Molecular Impact of BCL6 Gene Rearrangement in Most Prevalent Non-Hodgkin Lymphomas
- ClinicalTrials.gov ID
- NCT06424379
- Acronym / sponsor ID
- BCL6-RINHL / 69HCL24_0515
- Conditions
- Non Hodgkin Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Diffuse Large B Cell Lymphoma
- Keywords
- Non Hodgkin Lymphoma, BCL6 gene rearrangement, Next generation sequencing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 22 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.
Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.
A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.
FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.
MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.
Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Follicular lymphomas with BCL6 gene rearrangement | – | Other: Histopathological analysis, Genetic: Molecular analysisDiagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. |
| Marginal zone lymphomas with BCL6 gene rearrangement | – | Other: Histopathological analysis, Genetic: Molecular analysisDiagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. |
| Diffuse large B-cells lymphomas with BCL6 gene rearrangement | – | Other: Histopathological analysis, Genetic: Molecular analysisDiagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols. |
Who may qualify
- Ages
- 25 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients diagnosed with non-Hodgkin lymphoma from the routine diagnostic archives of the pathology department of CHU Lyon Sud between January 2016 and August 2023 and with BCL6-R detected by FISH analysis will be included in the study. A cohort of 135 cases will be assembled and subjected to the analysis. This dataset will be reviewed by two haematopathologists to ensure the inclusion of the most relevant cases. Selection will favor cases with substantial histological material and available clinical, immunophenotypic and cytogenetic data. Comparative assessments will be conducted between distinct subtypes of NHL exhibiting BCL6-R, including FLs, MZLs, and DLBCLs.
Key inclusion criteria (3 listed)
- Diagnostic of non-Hodgkin's lymphoma at anatomy and cytology department of Lyon Sud hospital
- Rearrangement of the BCL6 gene detected by FISH analysis
- Diagnostic of the disease between january 2016 and december 2023
Key exclusion criteria (3 listed)
- Patients diagnosed with primary cutaneous centrofollicular B lymphoma, composite lymphoma, anaplastic B lymphoma or primary B lymphoma of the mediastinum.
- Presence of a rearrangement of the BLC2 gene or the CMYC gene in FISH
- Presence of a non-significant BCL6 gene rearrangement (<5% of rearranged cells)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Histopathological analysisMorphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm. | Other | Diffuse large B-cells lymphomas with BCL6 gene rearrangement, Follicular lymphomas with BCL6 gene rearrangement, Marginal zone lymphomas with BCL6 gene rearrangement |
| Molecular analysisNext-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels. RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL). | Genetic | Diffuse large B-cells lymphomas with BCL6 gene rearrangement, Follicular lymphomas with BCL6 gene rearrangement, Marginal zone lymphomas with BCL6 gene rearrangement |
Primary outcome
Comparison of LF and MZL with BCL6-R.
Time frame: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.
Comparison of LF and MZL with BCL6-R.
Time frame: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non Hodgkin Lymphoma and Follicular Lymphoma, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of LF and MZL with BCL6-R. (time frame: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2024.