<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/NCT04468841</url>
  </required_header>
  <id_info>
    <org_study_id>20-199</org_study_id>
    <nct_id>NCT04468841</nct_id>
  </id_info>
  <brief_title>Measuring Cell-Free DNA (cfDNA) Levels in People With Follicular Lymphoma</brief_title>
  <official_title>An Exploratory Study to Correlate the Level of Cell-free DNA With Response to First-line Treatment in Patients With Follicular Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The researchers are doing this study to measure and test cell-free DNA (cfDNA) in the blood&#xD;
      before, during, and after first-line treatment for follicular lymphoma. They will look at&#xD;
      whether cfDNA levels are related to a person's response to the usual first-line treatment for&#xD;
      follicular lymphoma. Researchers also want to understand how different genetic changes in&#xD;
      follicular lymphoma relate to a person's response to the usual first-line treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a non-therapeutic protocol aimed to assess the ability of the s cfDNA assay to detect&#xD;
      clinical response in FL when compared to conventional approaches for assessing response, such&#xD;
      as PET-CT scans.&#xD;
&#xD;
      Study assessments will include: 1) identification of the mutations present in the primary&#xD;
      tumor, 2) identification of these mutations in the peripheral blood samples collected before&#xD;
      initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of&#xD;
      induction therapy, and then every 6 months for a total of 2 years from the initiation of&#xD;
      therapy using a cfDNA assay. For patients who receive RT, peripheral blood samples will be&#xD;
      collected before initiation of RT, and then 3 months, 6 months, 12 months, 18 months and 24&#xD;
      months post RT using a s cfDNA assay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a non-therapeutic protocol. The intervention in this study will involve collection of a standard-of-care pre-treatment tumor biopsy (archival tissue, if available) to identify the tumor-specific s cfDNA signature.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>whether the assay can correctly identify presence of disease in patients with measurable disease</measure>
    <time_frame>2 years</time_frame>
    <description>Response will be evaluated using the updated response criteria entitled, &quot;The Lugano Classification&quot; system. The investigator will use of the 5-point scale for visually assessing response on the pre- and end-of-treatment FDGPET/CT scans. This scale is commonly referred to as the Deauville criteria; it was developed by international experts in the field at the First International Workshop on interim-PET in Lymphoma in Deauville in 2009 and is routinely applied to patients undergoing lymphoma directed therapy. The 5-point scale is described in the table below.&#xD;
1 No residual uptake 2 Uptake ≤ mediastinum 3 Uptake &gt; mediastinum but ≤ liver 4 Uptake moderately &gt; liver 5 Markedly increased uptake at any site or progression</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Follicular Lymphoma</condition>
  <arm_group>
    <arm_group_label>Prospective Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study participants with untreated, newly diagnosed follicular lymphoma will have blood collected for cfDNA testing before, during, and after their first-line treatment or observation period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Retrospective Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study participants who have received first-line treatment for follicular lymphoma and are in complete remission will have blood collected for cfDNA testing. In the retrospective cohort, MSKCC patients with CRs lasting ≥10 years after induction therapy will be studied. Initial tumor tissue (if available) will be collected to examine the status of s cfDNA in patients with long-term remissions. Blood samples will be collected once, if the patient has interesting results (e.g. positive cfDNA sample despite CR on imaging, etc.) then additional blood samples may be taken during follow up visits.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>cfDNA testing</intervention_name>
    <description>peripheral blood samples collected before initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of induction therapy, and then every 6 months for a total of 2 years from the initiation of therapy using a cfDNA assay. For retrospective patients, blood samples will be collected once.</description>
    <arm_group_label>Prospective Group</arm_group_label>
    <arm_group_label>Retrospective Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>sample of saliva or fingernail clipping</intervention_name>
    <description>collected in clinic one time</description>
    <arm_group_label>Prospective Group</arm_group_label>
    <arm_group_label>Retrospective Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>pre-treatment test specimen</intervention_name>
    <description>From bone marrow, blood, lymph node, or alternate site to identify tumor-specific mutations. For retrospective patients initial tumor tissue (if available).</description>
    <arm_group_label>Prospective Group</arm_group_label>
    <arm_group_label>Retrospective Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PET/CT, CT, or MRI testing</intervention_name>
    <description>PET/CT scans are required at baseline and at the patient's end-of-treatment visit. The other standard-of-care scan timepoints can be performed using PET/CT, dedicated CT, or MRI per the treating investigator's discretion.</description>
    <arm_group_label>Prospective Group</arm_group_label>
    <arm_group_label>Retrospective Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥18 years of age at time of signing informed consent. Consent is permitted from either&#xD;
             the participant or from a Legally Authorized Representative (LAR) on their behalf.&#xD;
&#xD;
          -  Histology-confirmed follicular lymphoma grade 1-3a, verified by the enrolling&#xD;
             institution&#xD;
&#xD;
          -  Ability to adhere to the study visit schedule and all the protocol requirements&#xD;
&#xD;
          -  Measurable FDG-avid disease&#xD;
&#xD;
          -  Not applicable for retrospective patients in CR&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving second or greater line of therapy (except in retrospective cohort&#xD;
             of long-term survivors of FL [i.e. &gt;10 years out from frontline treatment])&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paola Ghione, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paola Ghione, MD</last_name>
    <phone>646-608-4263</phone>
    <email>ghionep@mskcc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria Arcila, MD</last_name>
    <phone>212-639-7879</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (All Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (All protocol activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (All protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (All Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (All Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
    <contact_backup>
      <last_name>Maria Arcila, MD</last_name>
      <phone>212-639-7879</phone>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (All Protocol Activities)</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paola Ghione, MD</last_name>
      <phone>646-608-4263</phone>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cell-free DNA</keyword>
  <keyword>20-199</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT04468841
org study id: 20-199
nct id: NCT04468841
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The researchers are doing this study to measure and test cell-free DNA (cfDNA) in the blood
      before, during, and after first-line treatment for follicular lymphoma. They will look at
      whether cfDNA levels are related to a person's response to the usual first-line treatment for
      follicular lymphoma. Researchers also want to understand how different genetic changes in
      follicular lymphoma relate to a person's response to the usual first-line treatment.
This is a non-therapeutic protocol aimed to assess the ability of the s cfDNA assay to detect
      clinical response in FL when compared to conventional approaches for assessing response, such
      as PET-CT scans.

      Study assessments will include: 1) identification of the mutations present in the primary
      tumor, 2) identification of these mutations in the peripheral blood samples collected before
      initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of
      induction therapy, and then every 6 months for a total of 2 years from the initiation of
      therapy using a cfDNA assay. For patients who receive RT, peripheral blood samples will be
      collected before initiation of RT, and then 3 months, 6 months, 12 months, 18 months and 24
      months post RT using a s cfDNA assay.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This is a non-therapeutic protocol. The intervention in this study will involve collection of a standard-of-care pre-treatment tumor biopsy (archival tissue, if available) to identify the tumor-specific s cfDNA signature.
primary purpose: Diagnostic
masking: None (Open Label)
measure: whether the assay can correctly identify presence of disease in patients with measurable disease
time frame: 2 years
description: Response will be evaluated using the updated response criteria entitled, "The Lugano Classification" system. The investigator will use of the 5-point scale for visually assessing response on the pre- and end-of-treatment FDGPET/CT scans. This scale is commonly referred to as the Deauville criteria; it was developed by international experts in the field at the First International Workshop on interim-PET in Lymphoma in Deauville in 2009 and is routinely applied to patients undergoing lymphoma directed therapy. The 5-point scale is described in the table below.
1 No residual uptake 2 Uptake ≤ mediastinum 3 Uptake > mediastinum but ≤ liver 4 Uptake moderately > liver 5 Markedly increased uptake at any site or progression
arm group label: Prospective Group
arm group type: Experimental
description: Study participants with untreated, newly diagnosed follicular lymphoma will have blood collected for cfDNA testing before, during, and after their first-line treatment or observation period
arm group label: Retrospective Group
arm group type: Experimental
description: Study participants who have received first-line treatment for follicular lymphoma and are in complete remission will have blood collected for cfDNA testing. In the retrospective cohort, MSKCC patients with CRs lasting ≥10 years after induction therapy will be studied. Initial tumor tissue (if available) will be collected to examine the status of s cfDNA in patients with long-term remissions. Blood samples will be collected once, if the patient has interesting results (e.g. positive cfDNA sample despite CR on imaging, etc.) then additional blood samples may be taken during follow up visits.
intervention type: Diagnostic Test
intervention name: cfDNA testing
description: peripheral blood samples collected before initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of induction therapy, and then every 6 months for a total of 2 years from the initiation of therapy using a cfDNA assay. For retrospective patients, blood samples will be collected once.
arm group label: Prospective Group
arm group label: Retrospective Group
intervention type: Other
intervention name: sample of saliva or fingernail clipping
description: collected in clinic one time
arm group label: Prospective Group
arm group label: Retrospective Group
intervention type: Diagnostic Test
intervention name: pre-treatment test specimen
description: From bone marrow, blood, lymph node, or alternate site to identify tumor-specific mutations. For retrospective patients initial tumor tissue (if available).
arm group label: Prospective Group
arm group label: Retrospective Group
intervention type: Diagnostic Test
intervention name: PET/CT, CT, or MRI testing
description: PET/CT scans are required at baseline and at the patient's end-of-treatment visit. The other standard-of-care scan timepoints can be performed using PET/CT, dedicated CT, or MRI per the treating investigator's discretion.
arm group label: Prospective Group
arm group label: Retrospective Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paola Ghione, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Paola Ghione, MD
phone: 646-608-4263
email: ghionep@mskcc.org
last name: Maria Arcila, MD
phone: 212-639-7879
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.