DLBCLSMOLYNCT03672682
SMOLY : Phenotype and Functions of Monocyte Subtypes in High Grade B Lymphoma: Towards New Biomarkers?
An observational study of DLBCL, run by Rennes University Hospital at 1 site in France.
Trial summary
Large-cell B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and accounts for about 40% of new cases. Although the DLBCL is a single entity in the WHO classification, several subgroups with different prognoses are recognized. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- DLBCL
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- 1 Sep 2017to 1 Sep 2019
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy. Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment. Group 3: 15 healthy patients.
Who may be able to join
- Age> or equal to 18 years and <or equal to 70 years
- Large cell diffuse NHL B (WHO)
- Stage I - II bulky with tumor mass> 7cm or stage III or IV of the Ann Arbor classification
- No prior treatment (even corticosteroid therapy)
- HIV negative
- Informed consent signed
- Patient follow-up> 2 years after completion of first-line treatment
Who cannot join
- Age <18 years or> 70 years
- Aggressive transformation of a known low-grade NHL
- Primary CNS Lymphoma
- MALT transformed lymphoma or Burkitt's lymphoma
- Lymphoma post transplantation
- Stage I or II with tumor mass <or equal to 7cm
Show all 13Show fewer
- Cancer with the exception of carcinoma in situ of the cervix or non-invasive cutaneous epithelium
- History of cured cancer treated systematically and / or causing secondary complications in the six months prior to inclusion in the protocol
- Pre-treatment
- HIV positive
- Patient with a disability who does not have a good understanding of informed consent
- Unsigned informed consent
- Patient follow-up <2 years after completion of first-line treatment
Trial locations and contacts
1 site in 1 country.
About this study
Large-cell B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and accounts for about 40% of new cases. Although the DLBCL is a single entity in the WHO classification, several subgroups with different prognoses are recognized. These subgroups take into account the tumor localization (primitive cerebral lymphoma, serous lymphoma, intravascular or exclusive lymph node) or a particular molecular signature (GCB profile, germline center B cell or ABC, activated B cell). Despite the introduction of immunotherapy, treatment failures are common. Overall survival at 5 years is estimated to be between 26 and 73%. This highlights the important heterogeneity of this pathology and therefore the need for biomarkers prognosis. Recently, an increase in monocytes in the blood of DLBCL patients has been proposed as a prognostic factor for independent survival. This marker of poor prognosis is also found in many solid.
Monocytes are effectors of the inflammatory response. They have different functional profiles depending on the level of expression of CD14 and CD16. Four subtypes of monocytes are distinguished: classical (CD14posCD16neg), intermediate (CD14posCD16pos) and non-classical (CD14lowCD16pos); the latter population is divided into two sub-groups depending on the expression of the SLAN protein. The different monocytic subpopulations have very diverse functions ranging from an immunosuppressive profile to an activation of the immune system. CD14posCD16neg monocytes are specialized in phagocytosis, production of oxygen derivatives (ROS) and pro-inflammatory cytokine secretion in response to microbial infection. CD14dimCD16pos monocytes are specialized in immune surveillance and produce proinflammatory cytokines such as TNFα and IL-1β in response to LPS stimulation.7 The Slanpos subpopulation produces IL-12 and thus has pro-inflammatory properties. Finally, CD14posCD16pos monocytes have controversial functions. For some authors, they produce the immunomodulatory cytokine IL-10, inhibit the proliferation of CD4 T lymphocytes and induce the recruitment of regulatory T lymphocytes, while for others they produce TNF-α, a pro- inflammatory.From a practical point of view CD14 and CD16 expression forms a continuum, which translates into complexity in the phenotypic definition of these cells and explains the contradictory data on their functionalities. Interestingly, in a laboratory work and in the course of publication, this fraction is increased in the blood of DLBCL patients compared to healthy donors (manuscript in preparation), on the contrary the monocytic fraction CD14dimCD16 pos is decreased in these patients.
Read more
In the end, if the increase in monocytes is known to be poor prognosis in patients with DLBCL, the monocyte fraction involved and the monocytic functions involved in this phenomenon are not known.
Since 2011, the Clinical and Biological Hematology Services have a database from a research protocol (BMS_LyTrans). This protocol includes patients with DLBCL as well as healthy patients, in order to allow the biological characterization of biomarkers in this pathology. Thus, we have blood samples and analysis of certain monocyte subtypes by flow cytometry at diagnosis, in more than 100 patients with DLBCL.
Read the detailed description
Primary objective :
Describe and compare the distribution of the different monocytic subpopulations according to the chemosensitivity profile (group 1) or chemoresistance (group 2) of patients with DLBCL and healthy donors (group 3), and identify their specific functionalities.
Secondary objective :
To determine the prognostic impact in terms of progression-free survival (EFS) of the distribution of the monocytic sub-population (s) defined i during the primary objective, in a retrospective study (BMS Ly Trans)
Design/Methodology : Retrospective, observational, monocentric study.
- - Part 1: Phenotypic and functional study of monocytic sub - populations of patients with DLBCL.
- Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy. Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment. Group 3: 15 healthy patients. A - Irish Lab (Nashville)
- Phenotypic analysis by mass cytometry: This new technology allows the integration of multiple data with membrane markers, intracytoplasmic proteins as well as transcription factors, thus providing global modeling of signaling pathways B - UMR 917 (Rennes) 8 months Cell sorting: The four subtypes of monocytes described above will be sorted by flow cytometry according to the expression of CD14, CD16 and Slan.
- High-throughput transcriptional analysis: cell lysis and real-time PCR in order to study the expression of genes involved in the mechanisms of immunomodulation.Bio-informatics, Integrated analysis: The set of clinical, transcriptomic and proteomic data will be analyzed in an integrated way using tools and algorithms working within the Irish lab.
- - 2nd part (Rennes) - 6 months : Populations differentially expressed between groups in part 1 will be analyzed on a cohort of 100 samples. These parameters will be analyzed jointly after integration in a database, uni- and multivariate analysis and the survival probability will be calculated for groups with a log-rank test.
Expected benefits :
- - To allow a better understanding of the monocyte compartment in DLBCL, particularly with regard to the immunosuppressive capacity of some of these cellular subtypes.
- - To refine the interest of the biomarker "monocyte level" on EFS in patients with DLBCL, highlighting the monocyte subtype involved.
- - To continue the collaboration between the two sites, which will allow to combine technologies and expertise present in Rennes (patient recruitment, cell sorting, molecular analysis (Biomark)) or in Nashville (CyTOF, bioinformatics, integrated analysis).
- Conditions
- DLBCL
- Keywords
- DLBCL, chemosensitivity, chemoresistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| DLBCL with chemoresistance | 15 patients with DLBCL with chemoresistance or relapsed less than 2 years after completion of first-line therapy | |
| DLBCL with chemosensitivity | 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line therapy. | |
| Healthy patients | 15 healthy patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of monocytic sub-population(s)
Increased proportion of one or more monocytic sub-populations (s) and / or modulation of the markers tested in one of the three groups studied.
Measured: At inclusion
Secondary outcomes (1)
Progression-free survival
Difference of EFS in the validation cohort between patients with DLBCL having an increased proportion of one or more monocytic subpopulation (s) or modulation of the markers suspected in the descriptive phase, and the others.
Measured: 2 years post diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2018
- Study start1 Sep 2017
- Primary completion1 Sep 2019
- Study completion1 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DLBCLStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe 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
- Other
- Time perspective
- Retrospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03672682
- Sponsor's protocol ID
- 35RC16_9799_SMOLY
- Other IDs
- 16.40, 2043484
- Acronym
- SMOLY
- Status last verified
- Nov 2019
- First submitted
- 10 Oct 2017
- Last updated
- 6 Nov 2019
- 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 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMOLY : Phenotype and Functions of Monocyte Subtypes in High Grade B Lymphoma: Towards New Biomarkers?
- ClinicalTrials.gov ID
- NCT03672682
- Acronym / sponsor ID
- SMOLY / 35RC16_9799_SMOLY
- Conditions
- DLBCL
- Keywords
- DLBCL, chemosensitivity, chemoresistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Vanderbilt University
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Sep 2019 (actual)
- First posted
- 14 Sep 2018 (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.
Large-cell B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and accounts for about 40% of new cases. Although the DLBCL is a single entity in the WHO classification, several subgroups with different prognoses are recognized. These subgroups take into account the tumor localization (primitive cerebral lymphoma, serous lymphoma, intravascular or exclusive lymph node) or a particular molecular signature (GCB profile, germline center B cell or ABC, activated B cell). Despite the introduction of immunotherapy, treatment failures are common. Overall survival at 5 years is estimated to be between 26 and 73%. This highlights the important heterogeneity of this pathology and therefore the need for biomarkers prognosis. Recently, an increase in monocytes in the blood of DLBCL patients has been proposed as a prognostic factor for independent survival. This marker of poor prognosis is also found in many solid.
Monocytes are effectors of the inflammatory response. They have different functional profiles depending on the level of expression of CD14 and CD16. Four subtypes of monocytes are distinguished: classical (CD14posCD16neg), intermediate (CD14posCD16pos) and non-classical (CD14lowCD16pos); the latter population is divided into two sub-groups depending on the expression of the SLAN protein. The different monocytic subpopulations have very diverse functions ranging from an immunosuppressive profile to an activation of the immune system. CD14posCD16neg monocytes are specialized in phagocytosis, production of oxygen derivatives (ROS) and pro-inflammatory cytokine secretion in response to microbial infection. CD14dimCD16pos monocytes are specialized in immune surveillance and produce proinflammatory cytokines such as TNFα and IL-1β in response to LPS stimulation.7 The Slanpos subpopulation produces IL-12 and thus has pro-inflammatory properties. Finally, CD14posCD16pos monocytes have controversial functions. For some authors, they produce the immunomodulatory cytokine IL-10, inhibit the proliferation of CD4 T lymphocytes and induce the recruitment of regulatory T lymphocytes, while for others they produce TNF-α, a pro- inflammatory.From a practical point of view CD14 and CD16 expression forms a continuum, which translates into complexity in the phenotypic definition of these cells and explains the contradictory data on their functionalities. Interestingly, in a laboratory work and in the course of publication, this fraction is increased in the blood of DLBCL patients compared to healthy donors (manuscript in preparation), on the contrary the monocytic fraction CD14dimCD16 pos is decreased in these patients.
In the end, if the increase in monocytes is known to be poor prognosis in patients with DLBCL, the monocyte fraction involved and the monocytic functions involved in this phenomenon are not known.
Since 2011, the Clinical and Biological Hematology Services have a database from a research protocol (BMS_LyTrans). This protocol includes patients with DLBCL as well as healthy patients, in order to allow the biological characterization of biomarkers in this pathology. Thus, we have blood samples and analysis of certain monocyte subtypes by flow cytometry at diagnosis, in more than 100 patients with DLBCL.
Detailed description
Primary objective :
Describe and compare the distribution of the different monocytic subpopulations according to the chemosensitivity profile (group 1) or chemoresistance (group 2) of patients with DLBCL and healthy donors (group 3), and identify their specific functionalities.
Secondary objective :
To determine the prognostic impact in terms of progression-free survival (EFS) of the distribution of the monocytic sub-population (s) defined i during the primary objective, in a retrospective study (BMS Ly Trans)
Design/Methodology : Retrospective, observational, monocentric study.
- - Part 1: Phenotypic and functional study of monocytic sub - populations of patients with DLBCL.
- Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy. Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment. Group 3: 15 healthy patients. A - Irish Lab (Nashville)
- Phenotypic analysis by mass cytometry: This new technology allows the integration of multiple data with membrane markers, intracytoplasmic proteins as well as transcription factors, thus providing global modeling of signaling pathways B - UMR 917 (Rennes) 8 months Cell sorting: The four subtypes of monocytes described above will be sorted by flow cytometry according to the expression of CD14, CD16 and Slan.
- High-throughput transcriptional analysis: cell lysis and real-time PCR in order to study the expression of genes involved in the mechanisms of immunomodulation.Bio-informatics, Integrated analysis: The set of clinical, transcriptomic and proteomic data will be analyzed in an integrated way using tools and algorithms working within the Irish lab.
- - 2nd part (Rennes) - 6 months : Populations differentially expressed between groups in part 1 will be analyzed on a cohort of 100 samples. These parameters will be analyzed jointly after integration in a database, uni- and multivariate analysis and the survival probability will be calculated for groups with a log-rank test.
Expected benefits :
- - To allow a better understanding of the monocyte compartment in DLBCL, particularly with regard to the immunosuppressive capacity of some of these cellular subtypes.
- - To refine the interest of the biomarker "monocyte level" on EFS in patients with DLBCL, highlighting the monocyte subtype involved.
- - To continue the collaboration between the two sites, which will allow to combine technologies and expertise present in Rennes (patient recruitment, cell sorting, molecular analysis (Biomark)) or in Nashville (CyTOF, bioinformatics, integrated analysis).
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DLBCL with chemoresistance | – | –15 patients with DLBCL with chemoresistance or relapsed less than 2 years after completion of first-line therapy |
| DLBCL with chemosensitivity | – | –15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line therapy. |
| Healthy patients | – | –15 healthy patients |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patient selection from the BMS_LyTrans database : Group 1: 15 patients with DLBCL with chemoresistance or relapse less than 2 years after completion of first-line therapy. Group 2: 15 patients with DLBCL with chemosensitivity without relapse within 2 years following the end of first-line treatment. Group 3: 15 healthy patients.
Key inclusion criteria (7 listed)
- Age> or equal to 18 years and <or equal to 70 years
- Large cell diffuse NHL B (WHO)
- Stage I - II bulky with tumor mass> 7cm or stage III or IV of the Ann Arbor classification
- No prior treatment (even corticosteroid therapy)
- HIV negative
Key exclusion criteria (13 listed)
- Age <18 years or> 70 years
- Aggressive transformation of a known low-grade NHL
- Primary CNS Lymphoma
- MALT transformed lymphoma or Burkitt's lymphoma
- Lymphoma post transplantation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proportion of monocytic sub-population(s)
Time frame: At inclusion
Increased proportion of one or more monocytic sub-populations (s) and / or modulation of the markers tested in one of the three groups studied.
1 secondary outcome
Progression-free survival
Time frame: 2 years post diagnosis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
- 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 DLBCL, run by Rennes University Hospital 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 7 inclusion and 13 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: finished, as of the sponsor's last update on 6 Nov 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of monocytic sub-population(s) (time frame: At inclusion). 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 6 Nov 2019.