Follicular LymphomaCONPILNCT03234140
Constitutional Genetics in Follicular Lymphoma
An observational study of Follicular Lymphoma and Genetic Predisposition to Disease, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never develop Follicular lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Follicular Lymphoma, Genetic Predisposition to Disease
- What is being tested?
- Genome Wide Association Studies and Single-nucleotide polymorphisms's genotyping
- How many people
- 1,883 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2017to Nov 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Group "Genome Wide Association Studies" : Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte : * PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396 * RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441 * FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229 * MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178 * MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321 Group "EPIC" : Patients are adults, male or female, included in the EPIC Cohort (European Prospective Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon, France).
Who may be able to join
- Follicular lymphoma treated in first line therapy treated by immunochemotherapy (PRIMA, FOL05, MER1 and 2, control arm of RELEVANCE trial)
- Follicular lymphoma treated in first line therapy by Rituximab and Lenalidomide as part of the investigational arm of RELEVANCE trial
- Available constitutional DNA samples for GWAS analysis with an accurate consent form for such genetic study
- Available biological and clinical characteristics at diagnosis with a follow-up of the patient for event free survival analysis
- 18 years of age or older
- Included in the EPIC Cohort (European Prospective Investigation into Cancer and nutrition study between 1992 and 2000)
- Available constitutional DNA samples with an accurate consent form for such genetic study
- 18 years of age or older
Who cannot join
- A non-follicular lymphoma histology according to WHO 2016 classification (grade 1, 2, 3a follicular lymphoma)
- Relapsed follicular lymphoma
- Patients without an accurate consent form for constitutional genetic study
- Patients with no available biological or clinical data and follow-up for the outcome analysis
- Group "EPIC"
- Patients without an accurate consent form for constitutional genetic study
- Patients with no available biological or clinical data and follow-up for the outcome analysis
Trial locations and contacts
1 site in 1 country.
France1 site
Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
Pierre-Bénite, 69495
Hervé Ghesquières, Pr, 04 78 86 43 01 ext. +33, herve.ghesquieres@chu-lyon.fr
Hervé Ghesquières, Pr
About this study
Official title: Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma
Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never develop Follicular lymphoma. It was observed that individuals who developed Follicular lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol 2014). High t(14;18) frequency in blood from healthy individuals could be a predictive biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells as well as failure of the micro-environment to control the proliferation of these cells are proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis of Follicular lymphoma patients has been significantly improved mainly with the development of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years. However, this lymphoma remains an incurable disease. The most commonly used tool for prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology.
Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. The investigators also plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk Follicular lymphoma individuals.
- Being tested
- Genome Wide Association Studies, Single-nucleotide polymorphisms's genotyping
- Medical subject headings
- Lymphoma, Follicular, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genome Wide Association StudiesGenetic
Using the Genome wide association studies (GWAS) approach on these 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data.
Single-nucleotide polymorphisms's genotypingGenetic
Analyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels
| Study group | Role | What they receive |
|---|---|---|
| Group "Genome Wide Association Studies" | Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte :
* PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396
* RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441
* FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229
* MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178
* MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321
Using the Genome wide association studies (GWAS) approach on these 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. Receives: Genetic: Genome Wide Association Studies | |
| Group "EPIC" | Patients are adults, male or female, included in the EPIC Cohort (European Prospective Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon, France).
The investigators plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in these 318 healthy individuals including 100 who will develop follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk follicular lymphoma individuals. Receives: Genetic: Single-nucleotide polymorphisms's genotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
Event Free Survival for follicular lymphoma patients treated with modern immunochemotherapy in five cohorts is the primary end point defined as the time from the diagnosis or randomization to the date of progression, relapse, re-treatment, or death from any cause.
Two steps analysis, with a discovery cohort and a validation cohort :
The discovery cohorts that the investigators plan to study are a subset of patients with available deoxyribonucleic acid samples of two prospective phase III trials (PRIMA (NCT00140582) (N=396) and FOLL-05 (NCT00774826) (N=229), and one prospective observational cohort SPORE of the University of Iowa-Mayo Clinic (MER1; N=178). A GWAS will then be performed on a subset of patients with available deoxyribonucleic acid of two validation cohorts (Prospective observational SPORE MER2; N=321, phase III trial RELEVANCE, NCT01476787, N=441).
Measured: 1 year
Secondary outcomes (1)
Somatic alterations and tumor biology
In order to better decipher the impact of host genetics on somatic alterations and tumor biology and understand the physiological function of the single-nucleotide polymorphism identified from the primary outcome measure, we will study the link between the molecular profiles of the tumor and the prognostic single-nucleotide polymorphism. This will be performed on samples of the PRIMA and MER studies, for which we have access to somatic and constitutive data.
In parallel, we will investigate the relation between known susceptibility single-nucleotide polymorphism and the level of the t(14 ;18) translocation. The latter analysis will be performed on EPIC samples (European Prospective Investigation Into Cancer and Nutrition), comparing healthy individuals to individuals who developed a follicular lymphoma. Finally, we will assess the effect of susceptibility single-nucleotide polymorphism on somatic molecular profiles on PRIMA and MAYO cohorts.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study startNov 2017 (estimated)
- Primary completionJul 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular 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
- 1,883 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
- NCT03234140
- Sponsor's protocol ID
- 69HCL17_0212
- Acronym
- CONPIL
- Status last verified
- Jul 2017
- First submitted
- 26 Jul 2017
- Last updated
- 31 Jul 2017
- 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 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT03234140
- Acronym / sponsor ID
- CONPIL / 69HCL17_0212
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,883 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Nov 2017 (estimated)
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 31 Jul 2017 (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.
Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never develop Follicular lymphoma. It was observed that individuals who developed Follicular lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol 2014). High t(14;18) frequency in blood from healthy individuals could be a predictive biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells as well as failure of the micro-environment to control the proliferation of these cells are proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis of Follicular lymphoma patients has been significantly improved mainly with the development of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years. However, this lymphoma remains an incurable disease. The most commonly used tool for prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology.
Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. The investigators also plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk Follicular lymphoma individuals.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group "Genome Wide Association Studies" | – | Genetic: Genome Wide Association StudiesPatients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte : * PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396 * RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441 * FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229 * MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178 * MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321 Using the Genome wide association studies (GWAS) approach on these 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. |
| Group "EPIC" | – | Genetic: Single-nucleotide polymorphisms's genotypingPatients are adults, male or female, included in the EPIC Cohort (European Prospective Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon, France). The investigators plan to analyze the influence of single-nucleotide polymorphisms on circulating t(14;18) levels in these 318 healthy individuals including 100 who will develop follicular lymphoma later on, and assess if these biomarkers are helpful to refine the identification of high-risk follicular lymphoma individuals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Group "Genome Wide Association Studies" : Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte : * PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396 * RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441 * FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229 * MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178 * MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321 Group "EPIC" : Patients are adults, male or female, included in the EPIC Cohort (European Prospective Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon, France).
Key inclusion criteria (8 listed)
- Follicular lymphoma treated in first line therapy treated by immunochemotherapy (PRIMA, FOL05, MER1 and 2, control arm of RELEVANCE trial)
- Follicular lymphoma treated in first line therapy by Rituximab and Lenalidomide as part of the investigational arm of RELEVANCE trial
- Available constitutional DNA samples for GWAS analysis with an accurate consent form for such genetic study
- Available biological and clinical characteristics at diagnosis with a follow-up of the patient for event free survival analysis
- 18 years of age or older
Key exclusion criteria (7 listed)
- A non-follicular lymphoma histology according to WHO 2016 classification (grade 1, 2, 3a follicular lymphoma)
- Relapsed follicular lymphoma
- Patients without an accurate consent form for constitutional genetic study
- Patients with no available biological or clinical data and follow-up for the outcome analysis
- Group "EPIC"
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 |
|---|---|---|
| Genome Wide Association StudiesUsing the Genome wide association studies (GWAS) approach on these 1,565 patients, the project plan to identify new prognostic markers. These markers will then be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology, using public or matched patient data. | Genetic | Group "Genome Wide Association Studies" |
| Single-nucleotide polymorphisms's genotypingAnalyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels | Genetic | Group "EPIC" |
Primary outcome
Event Free Survival
Time frame: 1 year
Event Free Survival for follicular lymphoma patients treated with modern immunochemotherapy in five cohorts is the primary end point defined as the time from the diagnosis or randomization to the date of progression, relapse, re-treatment, or death from any cause. Two steps analysis, with a discovery cohort and a validation cohort : The discovery cohorts that the investigators plan to study are a subset of patients with available deoxyribonucleic acid samples of two prospective phase III trials (PRIMA (NCT00140582) (N=396) and FOLL-05 (NCT00774826) (N=229), and one prospective observational cohort SPORE of the University of Iowa-Mayo Clinic (MER1; N=178). A GWAS will then be performed on a subset of patients with available deoxyribonucleic acid of two validation cohorts (Prospective observational SPORE MER2; N=321, phase III trial RELEVANCE, NCT01476787, N=441).
1 secondary outcome
Somatic alterations and tumor biology
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- 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.
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 Follicular Lymphoma and Genetic Predisposition to Disease, 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 8 inclusion and 7 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 31 Jul 2017. 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?
Contact Hervé Ghesquières, Pr (04 78 86 43 01 ext. +33, herve.ghesquieres@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (time frame: 1 year). 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 31 Jul 2017.