Lymphoma Diffuse Large B-cellProLyPhy-GEPNCT03597685
Pesticide Associated Lymphomas: Expression of Treatment Resistance Genes
An observational study of Lymphoma Diffuse Large B-cell, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma Diffuse Large B-cell
- How many people
- 250 participants
- Where
- 1 siteFrance
- Study dates
- 20 Feb 2018to 31 Jan 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults treated for diffuse large B-cell lymphoma:
Who may be able to join
- Adults treated for diffuse large B-cell lymphoma:
- Diagnosed between 2010 and 2015
- Included in ProLyPhy search
- Having received R-CHOP immuno-chemotherapy
- Supported in health facilities in Languedoc-Rousillon
Who cannot join
- NA
Trial locations and contacts
1 site in 1 country.
About this study
Official title: ProLyPhy-GEP : Pesticide Associated Lymphomas: Expression of Treatment Resistance Genes
Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Parts of the mechanisms leading to NHL development after pesticide exposure are the disruption of immune surveillance against cancer cell. Pro-oncogenic action of metabolites is the most important mechanisms of action for pesticides. Thus, pesticides are metabolized in pro-oxidant compounds disturbing the redox homeostasis in the haematopoietic and immune cells precursors, promoting proliferation and survival, and inducing DNA breaks. Some of them induce direct DNA breaks and non-conform reparation, leading to activation of oncogenes; and other induces transcription factors for oncogenic signalling pathways. DNA reparation and adaptation to a higher ROS level are associated with resistance against cytotoxic chemotherapy treatment with induction of detoxification mechanism by tumour cells.
That DNA repair pathways, which are targeted by chemotherapy could also explain a part of chemo-resistance. It was therefore suggested that DLBCL dependence to specific DNA repair pathways could be targeted to hamper repair of intrinsic DNA damage occurring during B-lymphoma cells proliferation or to increase DNA damage induced by chemotherapy.
Read the detailed description
Occupational exposure to pesticides is associated with higher incidence of non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL) The relative risk for NHL after occupational exposure to pesticide is 1.5 to 3, with little variation according to NHL subtypes. DLBCL is one of the most frequent subtypes of NHL and characterized by aggressive presentation. DLBCL is treated by chemotherapy based on anthracyclines combined with an anti-CD20 monoclonal antibody allowing complete response and long term remission in 65-70% of patients. The response rate to treatment and clinical outcome is depending of the DLBCL subtype. There are 3 of them depending of the cell of origin (germinal centre B cell or activated B cell), and the anatomical location (primary mediastinal) identified by molecular gene expression profile. The activated B cell subtype have a worse outcome.
Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Parts of the mechanisms leading to NHL development after pesticide exposure are the disruption of immune surveillance against cancer cell. Pro-oncogenic action of metabolites is the most important mechanisms of action for pesticides. Thus, pesticides are metabolized in pro-oxidant compounds disturbing the redox homeostasis in the haematopoietic and immune cells precursors, promoting proliferation and survival, and inducing DNA breaks. Some of them induce direct DNA breaks and non-conform reparation, leading to activation of oncogenes; and other induces transcription factors for oncogenic signalling pathways. DNA reparation and adaptation to a higher ROS level are associated with resistance against cytotoxic chemotherapy treatment with induction of detoxification mechanism by tumour cells.
That DNA repair pathways, which are targeted by chemotherapy could also explain a part of chemo-resistance. It was therefore suggested that DLBCL dependence to specific DNA repair pathways could be targeted to hamper repair of intrinsic DNA damage occurring during B-lymphoma cells proliferation or to increase DNA damage induced by chemotherapy.
The investigators hypothesize that actions of pesticides on DNA and redox homeostasis are critical events during lymphomagenesis. We supposed that specific mechanisms of DNA repair and antioxidant defences induced by pesticides exposure are implicated in the chemo-resistance in DLBCL patients.
There might be a negative impact of professional exposure to pesticide on treatment response.
In this search, the investigators will explore a comprehensive view of both lymphomagenesis and adverse prognosis of pesticide-exposed DLBCL. The investigators plan to analyse the molecular profile of B-lymphoma cells from pesticide-exposed patients, to better understand biological mechanisms underlying lymphomagenesis as well as chemotherapy resistance
- Conditions
- Lymphoma Diffuse Large B-cell
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What is being measured
The primary outcome is the main question the study is designed to answer.
genes implicated in chemoresistance of diffuse large B-cell lymphoma
Use of excesses of the biopsy made as part of the care for the diagnostic of the lymphoma for identify genes implicated in chemoresistance of DLBCL
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2018
- Study start20 Feb 2018
- Primary completion31 Dec 2018
- Study completion31 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoma Diffuse Large B-cellStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe 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
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sylvain LAMURE, CCA, Study director, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03597685
- Sponsor's protocol ID
- RECHMPL18_0010
- Acronym
- ProLyPhy-GEP
- Status last verified
- Mar 2019
- First submitted
- 16 Jan 2018
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: NC
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ProLyPhy-GEP : Pesticide Associated Lymphomas: Expression of Treatment Resistance Genes
- ClinicalTrials.gov ID
- NCT03597685
- Acronym / sponsor ID
- ProLyPhy-GEP / RECHMPL18_0010
- Conditions
- Lymphoma Diffuse Large B-cell
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 20 Feb 2018 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Jan 2019 (actual)
- First posted
- 24 Jul 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.
Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Parts of the mechanisms leading to NHL development after pesticide exposure are the disruption of immune surveillance against cancer cell. Pro-oncogenic action of metabolites is the most important mechanisms of action for pesticides. Thus, pesticides are metabolized in pro-oxidant compounds disturbing the redox homeostasis in the haematopoietic and immune cells precursors, promoting proliferation and survival, and inducing DNA breaks. Some of them induce direct DNA breaks and non-conform reparation, leading to activation of oncogenes; and other induces transcription factors for oncogenic signalling pathways. DNA reparation and adaptation to a higher ROS level are associated with resistance against cytotoxic chemotherapy treatment with induction of detoxification mechanism by tumour cells.
That DNA repair pathways, which are targeted by chemotherapy could also explain a part of chemo-resistance. It was therefore suggested that DLBCL dependence to specific DNA repair pathways could be targeted to hamper repair of intrinsic DNA damage occurring during B-lymphoma cells proliferation or to increase DNA damage induced by chemotherapy.
Detailed description
Occupational exposure to pesticides is associated with higher incidence of non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL) The relative risk for NHL after occupational exposure to pesticide is 1.5 to 3, with little variation according to NHL subtypes. DLBCL is one of the most frequent subtypes of NHL and characterized by aggressive presentation. DLBCL is treated by chemotherapy based on anthracyclines combined with an anti-CD20 monoclonal antibody allowing complete response and long term remission in 65-70% of patients. The response rate to treatment and clinical outcome is depending of the DLBCL subtype. There are 3 of them depending of the cell of origin (germinal centre B cell or activated B cell), and the anatomical location (primary mediastinal) identified by molecular gene expression profile. The activated B cell subtype have a worse outcome.
Lymphomagenesis is partially known, and some risk factor are identified like those inducing immune deficiencies: chronic exposure to HIV, immune suppressor therapies or commun variable immunodeficiency. Parts of the mechanisms leading to NHL development after pesticide exposure are the disruption of immune surveillance against cancer cell. Pro-oncogenic action of metabolites is the most important mechanisms of action for pesticides. Thus, pesticides are metabolized in pro-oxidant compounds disturbing the redox homeostasis in the haematopoietic and immune cells precursors, promoting proliferation and survival, and inducing DNA breaks. Some of them induce direct DNA breaks and non-conform reparation, leading to activation of oncogenes; and other induces transcription factors for oncogenic signalling pathways. DNA reparation and adaptation to a higher ROS level are associated with resistance against cytotoxic chemotherapy treatment with induction of detoxification mechanism by tumour cells.
That DNA repair pathways, which are targeted by chemotherapy could also explain a part of chemo-resistance. It was therefore suggested that DLBCL dependence to specific DNA repair pathways could be targeted to hamper repair of intrinsic DNA damage occurring during B-lymphoma cells proliferation or to increase DNA damage induced by chemotherapy.
The investigators hypothesize that actions of pesticides on DNA and redox homeostasis are critical events during lymphomagenesis. We supposed that specific mechanisms of DNA repair and antioxidant defences induced by pesticides exposure are implicated in the chemo-resistance in DLBCL patients.
There might be a negative impact of professional exposure to pesticide on treatment response.
In this search, the investigators will explore a comprehensive view of both lymphomagenesis and adverse prognosis of pesticide-exposed DLBCL. The investigators plan to analyse the molecular profile of B-lymphoma cells from pesticide-exposed patients, to better understand biological mechanisms underlying lymphomagenesis as well as chemotherapy resistance
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults treated for diffuse large B-cell lymphoma:
Key inclusion criteria (5 listed)
- Diagnosed between 2010 and 2015
- Included in ProLyPhy search
- Having received R-CHOP immuno-chemotherapy
- Supported in health facilities in Languedoc-Rousillon
Key exclusion criteria (1 listed)
- NA
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
genes implicated in chemoresistance of diffuse large B-cell lymphoma
Time frame: 1 day
Use of excesses of the biopsy made as part of the care for the diagnostic of the lymphoma for identify genes implicated in chemoresistance of DLBCL
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 18 Apr 2019.
- Individual participant dataSharing planned: Undecided. NC
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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.
Sylvain LAMURE, CCA study director
University Hospital, Montpellier
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 Lymphoma Diffuse Large B-cell, run by University Hospital, Montpellier 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 5 inclusion and 1 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 18 Apr 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?
genes implicated in chemoresistance of diffuse large B-cell lymphoma (time frame: 1 day). 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 18 Apr 2019.