<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03234140</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0212</org_study_id>
    <nct_id>NCT03234140</nct_id>
  </id_info>
  <brief_title>Constitutional Genetics in Follicular Lymphoma</brief_title>
  <acronym>CONPIL</acronym>
  <official_title>Constitutional Genetics to Predict Prognostic and Somatic Alterations in Follicular Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Follicular lymphoma is the second most common adult B-cell lymphoma. The acquisition of the&#xD;
      t(14;18) translocation is the genetic hallmark of Follicular lymphoma. However, 50% to 70% of&#xD;
      healthy individuals harbor low levels of circulating t(14;18)-positive cells but will never&#xD;
      develop Follicular lymphoma. It was observed that individuals who developed Follicular&#xD;
      lymphoma showed a higher t(14;18) frequency than controls (Roulland et al., J Clin Oncol&#xD;
      2014). High t(14;18) frequency in blood from healthy individuals could be a predictive&#xD;
      biomarker for Follicular lymphoma development. Genetic instability of those t(14;18)+ B-cells&#xD;
      as well as failure of the micro-environment to control the proliferation of these cells are&#xD;
      proposed mechanisms linking these lymphoma precursors to true lymphoma cells. The prognosis&#xD;
      of Follicular lymphoma patients has been significantly improved mainly with the development&#xD;
      of anti-CD20 monoclonal antibodies, with a current median overall survival over 15 years.&#xD;
      However, this lymphoma remains an incurable disease. The most commonly used tool for&#xD;
      prognostication of patients with Follicular lymphoma is the Follicular Lymphoma International&#xD;
      Prognostic Index (FLIPI) based on conventional clinical and pathology parameters. Although it&#xD;
      has clinical utility, the Follicular Lymphoma International Prognostic Index does not reflect&#xD;
      the biologic heterogeneity of Follicular lymphoma. First-degree relatives of Follicular&#xD;
      lymphoma had a fourfold increased risk of Follicular lymphoma suggesting a genetic etiology.&#xD;
&#xD;
      Using the Genome wide association studies (GWAS) approach on Follicular lymphoma cohorts of&#xD;
      1,565 patients, the project plan to identify new prognostic markers. These markers will then&#xD;
      be analyzed to decipher the impact of host genetics on somatic alterations and tumor biology,&#xD;
      using public or matched patient data. The investigators also plan to analyze the influence of&#xD;
      single-nucleotide polymorphisms on circulating t(14;18) levels in 318 healthy individuals&#xD;
      included in EPIC cohort that will develop Follicular lymphoma later on, and assess if these&#xD;
      biomarkers are helpful to refine the identification of high-risk Follicular lymphoma&#xD;
      individuals.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 2017</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Event Free Survival</measure>
    <time_frame>1 year</time_frame>
    <description>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.&#xD;
Two steps analysis, with a discovery cohort and a validation cohort :&#xD;
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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Somatic alterations and tumor biology</measure>
    <time_frame>2 years</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">1883</enrollment>
  <condition>Follicular Lymphoma</condition>
  <condition>Genetic Predisposition to Disease</condition>
  <arm_group>
    <arm_group_label>Group &quot;Genome Wide Association Studies&quot;</arm_group_label>
    <description>Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by immunochemotherapy included in one of the following cohorte :&#xD;
PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396&#xD;
RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441&#xD;
FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826): N=229&#xD;
MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987): N=178&#xD;
MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):N=321&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group &quot;EPIC&quot;</arm_group_label>
    <description>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).&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Genome Wide Association Studies</intervention_name>
    <description>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.</description>
    <arm_group_label>Group &quot;Genome Wide Association Studies&quot;</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Single-nucleotide polymorphisms's genotyping</intervention_name>
    <description>Analyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels</description>
    <arm_group_label>Group &quot;EPIC&quot;</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Group &quot;Genome Wide Association Studies&quot; :&#xD;
&#xD;
        Patients are adults, male or female, with a follicular lymphoma, homogeneously treated by&#xD;
        immunochemotherapy included in one of the following cohorte :&#xD;
&#xD;
          -  PRIMA Cohort : phase III (Sponsor LYSARC, France; NCT00140582): N=396&#xD;
&#xD;
          -  RELEVANCE Cohort : phase III (Sponsor LYSARC, France; NCT01476787 ): N=441&#xD;
&#xD;
          -  FOLL05 Cohort: phase III (Sponsor Italian lymphoma Foundation, Italy; NCT00774826):&#xD;
             N=229&#xD;
&#xD;
          -  MER1 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA; IRB#09-001987):&#xD;
             N=178&#xD;
&#xD;
          -  MER2 Cohorts : prospective, observational (Sponsor Mayo Clinic, USA;&#xD;
             IRB#09-001987):N=321&#xD;
&#xD;
        Group &quot;EPIC&quot; :&#xD;
&#xD;
        Patients are adults, male or female, included in the EPIC Cohort (European Prospective&#xD;
        Investigation Into Cancer and Nutrition study between 1992 and 2000. (Sponsor IARC, Lyon,&#xD;
        France).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Group &quot;Genome Wide Association Studies&quot;&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Follicular lymphoma treated in first line therapy treated by immunochemotherapy&#xD;
             (PRIMA, FOL05, MER1 and 2, control arm of RELEVANCE trial)&#xD;
&#xD;
          -  Follicular lymphoma treated in first line therapy by Rituximab and Lenalidomide as&#xD;
             part of the investigational arm of RELEVANCE trial&#xD;
&#xD;
          -  Available constitutional DNA samples for GWAS analysis with an accurate consent form&#xD;
             for such genetic study&#xD;
&#xD;
          -  Available biological and clinical characteristics at diagnosis with a follow-up of the&#xD;
             patient for event free survival analysis&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A non-follicular lymphoma histology according to WHO 2016 classification (grade 1, 2,&#xD;
             3a follicular lymphoma)&#xD;
&#xD;
          -  Relapsed follicular lymphoma&#xD;
&#xD;
          -  Patients without an accurate consent form for constitutional genetic study&#xD;
&#xD;
          -  Patients with no available biological or clinical data and follow-up for the outcome&#xD;
             analysis&#xD;
&#xD;
        Group &quot;EPIC&quot;&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Included in the EPIC Cohort (European Prospective Investigation into Cancer and&#xD;
             nutrition study between 1992 and 2000)&#xD;
&#xD;
          -  Available constitutional DNA samples with an accurate consent form for such genetic&#xD;
             study&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients without an accurate consent form for constitutional genetic study&#xD;
&#xD;
          -  Patients with no available biological or clinical data and follow-up for the outcome&#xD;
             analysis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hervé Ghesquières, Pr</last_name>
    <phone>04 78 86 43 01</phone>
    <phone_ext>+33</phone_ext>
    <email>herve.ghesquieres@chu-lyon.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Hervé Ghesquières, Pr</last_name>
      <phone>04 78 86 43 01</phone>
      <phone_ext>+33</phone_ext>
      <email>herve.ghesquieres@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Hervé Ghesquières, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>July 26, 2017</last_update_submitted>
  <last_update_submitted_qc>July 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Genetic Predisposition to Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03234140
org study id: 69HCL17_0212
nct id: NCT03234140
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Cohort
time perspective: Retrospective
measure: Event Free Survival
time frame: 1 year
description: 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).
measure: Somatic alterations and tumor biology
time frame: 2 years
description: 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.
arm group label: Group "Genome Wide Association Studies"
description: 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.
arm group label: Group "EPIC"
description: 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.
intervention type: Genetic
intervention name: Genome Wide Association Studies
description: 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.
arm group label: Group "Genome Wide Association Studies"
intervention type: Genetic
intervention name: Single-nucleotide polymorphisms's genotyping
description: Analyze of the influence of single-nucleotide polymorphisms on circulating t(14;18) levels
arm group label: Group "EPIC"
Peripheral blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Hervé Ghesquières, Pr
phone: 04 78 86 43 01
phone ext: +33
email: herve.ghesquieres@chu-lyon.fr
facility: 
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Genetic Predisposition to Disease
sharing ipd: No