<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/NCT03758989</url>
  </required_header>
  <id_info>
    <org_study_id>ULYM18040</org_study_id>
    <nct_id>NCT03758989</nct_id>
  </id_info>
  <brief_title>A Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</brief_title>
  <official_title>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overarching goals of this study are to measure levels of circulating tumor DNA (ctDNA) in&#xD;
      patients with early stage diffuse large B cell lymphoma (DLBCL), to assess the change in&#xD;
      ctDNA during treatment in order to prospectively identify markers of treatment failure, and&#xD;
      to use ctDNA as a future tool for response adapted therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The long-term objective of this proposal is to determine the correlation between FDG-PET and&#xD;
      MRD, as measured by ctDNA in patients with early stage DLBLC.&#xD;
&#xD;
      Patients will be treated with standard chemoimmunotherapy and radiation based on the recently&#xD;
      completed SWOG S1001 study, however no radioimmunotherapy will be used (NCT01359592).&#xD;
      Response to treatment will be determined by contemporary Deauville criteria. Assessment of&#xD;
      ctDNA (non-invasive disease monitoring) will be determined at diagnosis and will continue at&#xD;
      pre-defined specific time points after therapy is complete.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 8, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between fluorodeoxyglucose positron emission tomography (FDG-PET) and MRD, as measured by circulating tumor plasma DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL).</measure>
    <time_frame>5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>PET CR rate</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in minimal residual disease (MRD) from baseline to time of re-staging PET</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-staging Deauville score of 1, 2, or 3 (negative PET scan)</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Following 3 cycles of R-CHOP, if PET scan demonstrates complete response, defined by Deauville score of 1, 2, or 3 (negative PET scan), radiation therapy will not be required moving forward</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity rates using CTCAE v4.03</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in quality of life using PROMIS scale 10 scale will be administered to patients at the time of diagnosis, at the conclusion of all therapy, and at 12 month intervals</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) of patients through two years of follow-up.</measure>
    <time_frame>Patients will be assessed by physical exam and routine bloodwork every 3 months in the 1st year after conclusion of treatment, and every 6 months in the second year following treatment. They will be assessed yearly during years 3, 4 and 5.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From time of baseline scan through two years of follow-up</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>DLBCL</condition>
  <arm_group>
    <arm_group_label>Baseline PET</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>R-CHOP</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab Prednisone</intervention_name>
    <description>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</description>
    <arm_group_label>Baseline PET</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</description>
    <arm_group_label>Baseline PET</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</description>
    <arm_group_label>Baseline PET</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</description>
    <arm_group_label>Baseline PET</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma</description>
    <arm_group_label>Baseline PET</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previously untreated limited stage non bulky DLBCL; defined as limited stage by&#xD;
             routine staging criteria in lymphoma involving FDG-PET and bone marrow biopsies (the&#xD;
             Lugano criteria)[21]&#xD;
&#xD;
          -  Patients with grade 3B follicular lymphoma and transformed indolent lymphoma are&#xD;
             included&#xD;
&#xD;
          -  Ages ≥ 18&#xD;
&#xD;
          -  Measurable disease, assessable by radiographic examination with FDG-PET showing&#xD;
             involvement&#xD;
&#xD;
          -  Access to archived or fresh/frozen tumor biopsies&#xD;
&#xD;
          -  No uncontrolled medical comorbidities&#xD;
&#xD;
          -  Adequate cardiac function (EF &gt; or equal to 50%), no unstable angina&#xD;
&#xD;
          -  Adequate renal function (GFR &gt; 60)&#xD;
&#xD;
          -  Adequate liver function (liver function tests should be no greater than 2 x upper&#xD;
             limit of normal) including normal bilirubin levels, no greater than 2 x upper limit of&#xD;
             normal unless patient has a history of Gilbert's disease&#xD;
&#xD;
          -  Adequate marrow reserves as indicated by complete blood count in the judgment of the&#xD;
             treating investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, positive serum HCG within 28 days of enrollment, or breast-feeding&#xD;
&#xD;
          -  Bulky disease greater than 10 cm in any dimension&#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>Carla Casulo</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Robin Boerman</last_name>
    <phone>585-273-1507</phone>
    <email>Robin_Boerman@URMC.Rochester.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrew Bui</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 8, 2022</last_update_submitted>
  <last_update_submitted_qc>July 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Carla Casulo</investigator_full_name>
    <investigator_title>Associate Professor of Hematology/Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Vincristine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03758989
org study id: ULYM18040
nct id: NCT03758989
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The overarching goals of this study are to measure levels of circulating tumor DNA (ctDNA) in
      patients with early stage diffuse large B cell lymphoma (DLBCL), to assess the change in
      ctDNA during treatment in order to prospectively identify markers of treatment failure, and
      to use ctDNA as a future tool for response adapted therapy.
The long-term objective of this proposal is to determine the correlation between FDG-PET and
      MRD, as measured by ctDNA in patients with early stage DLBLC.

      Patients will be treated with standard chemoimmunotherapy and radiation based on the recently
      completed SWOG S1001 study, however no radioimmunotherapy will be used (NCT01359592).
      Response to treatment will be determined by contemporary Deauville criteria. Assessment of
      ctDNA (non-invasive disease monitoring) will be determined at diagnosis and will continue at
      pre-defined specific time points after therapy is complete.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Correlation between fluorodeoxyglucose positron emission tomography (FDG-PET) and MRD, as measured by circulating tumor plasma DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL).
time frame: 5 years
measure: PET CR rate
time frame: 5 years
measure: Change in minimal residual disease (MRD) from baseline to time of re-staging PET
time frame: 5 years
measure: Re-staging Deauville score of 1, 2, or 3 (negative PET scan)
time frame: 5 years
measure: Following 3 cycles of R-CHOP, if PET scan demonstrates complete response, defined by Deauville score of 1, 2, or 3 (negative PET scan), radiation therapy will not be required moving forward
time frame: 5 years
measure: Toxicity rates using CTCAE v4.03
time frame: 5 years
measure: Changes in quality of life using PROMIS scale 10 scale will be administered to patients at the time of diagnosis, at the conclusion of all therapy, and at 12 month intervals
time frame: 5 years
measure: Overall survival (OS) of patients through two years of follow-up.
time frame: Patients will be assessed by physical exam and routine bloodwork every 3 months in the 1st year after conclusion of treatment, and every 6 months in the second year following treatment. They will be assessed yearly during years 3, 4 and 5.
measure: Progression free survival (PFS)
time frame: From time of baseline scan through two years of follow-up
arm group label: Baseline PET
arm group type: Experimental
description: R-CHOP
intervention type: Drug
intervention name: Rituximab Prednisone
description: A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma
arm group label: Baseline PET
intervention type: Drug
intervention name: Cyclophosphamide
description: A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma
arm group label: Baseline PET
intervention type: Drug
intervention name: Doxorubicin
description: A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma
arm group label: Baseline PET
intervention type: Drug
intervention name: Vincristine
description: A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma
arm group label: Baseline PET
intervention type: Drug
intervention name: Prednisone
description: A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma
arm group label: Baseline PET
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carla Casulo
role: Principal Investigator
affiliation: University of Rochester
last name: Robin Boerman
phone: 585-273-1507
email: Robin_Boerman@URMC.Rochester.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Carla Casulo
investigator title: Associate Professor of Hematology/Oncology
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Vincristine
sharing ipd: Undecided