<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/NCT04499534</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 11119</org_study_id>
    <secondary_id>834194</secondary_id>
    <nct_id>NCT04499534</nct_id>
  </id_info>
  <brief_title>BRCA1/2 Flu Vaccine</brief_title>
  <official_title>Influenza Vaccine Study in BRCA1 or BRCA2 Carriers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</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>
      To evaluate immune function in BRCA1/2 mutation carriers without cancer, specifically to&#xD;
      determine whether immune function in healthy individuals with germline loss of function&#xD;
      BRCA1/2 mutations, impacts overall immune health and fitness.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 28, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate immune function in female BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination</measure>
    <time_frame>2 years</time_frame>
    <description>Analysis of the primary objective will depend on determination of the strain-specific neutralizing antibody titer change from day 0 to the last study visit, performed as the standard assay as described by the World Health Organization (WHO).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exploratory analysis- phenotypic evaluation of B cell</measure>
    <time_frame>2 years</time_frame>
    <description>Phenotypic evaluation of B and T cell responses to vaccine at each timepoint. Phenotypic analysis involves flow cytometry on peripheral blood mononuclear cells (PBMC) from all subjects (10 mL blood per subject).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory analysis - transcriptional evaluation</measure>
    <time_frame>2 years</time_frame>
    <description>Transcriptional evaluation of B and T cell responses to vaccine on day 7-10 timepoint. Transcriptional analyses including quantitative real-time PCR (RT-qPCR) and RNA sequencing (RNAseq) may be performed on a subset of the study subjects on the day 7-10 time point.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>BRCA1 Mutation</condition>
  <condition>BRCA2 Mutation</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Seasonal influenza vaccine</intervention_name>
    <description>To evaluate immune function in BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients 25 years and older, seen at Cancer Risk Evaluation Program (CREP) in the Perelman&#xD;
        Center for Advanced Medicine with BRCA1 or BRCA2 mutation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females&#xD;
&#xD;
          -  Over age 25&#xD;
&#xD;
          -  BRCA1 or BRCA2 pathogenic or likely pathogenic mutation&#xD;
&#xD;
          -  No personal cancer history apart from non melanoma skin cancer, localized thyroid&#xD;
             cancer, in situ cancers of any type&#xD;
&#xD;
          -  Participants must sign the informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are allergic to influenza vaccination&#xD;
&#xD;
          -  Have received influenza vaccination within the past 6 months&#xD;
&#xD;
          -  Require prednisone, methotrexate, or other immunosuppressing medications&#xD;
&#xD;
          -  Have HIV infection&#xD;
&#xD;
          -  Have a history of solid organ tumor or bone marrow transplant&#xD;
&#xD;
          -  Require combination immunotherapy;&#xD;
&#xD;
          -  Are on other studies requiring blood draws that might exceed 450 mL total during the&#xD;
             period of the influenza vaccine study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Domchek, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Susan Domchek, MD</last_name>
    <phone>215-615-3360</phone>
    <email>susan.domchek@pennmedicine.upenn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Heather Symecko, MPH</last_name>
    <phone>215-662-2770</phone>
    <email>hsymecko@pennmedicine.upenn.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Domchek, MD</last_name>
      <phone>215-615-3360</phone>
      <email>susan.domchek@pennmedicine.upenn.edu</email>
    </contact>
    <contact_backup>
      <last_name>Heather Symecko, MPH</last_name>
      <phone>215-662-2770</phone>
      <email>hsymecko@pennmedicine.upenn.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Susan Domchek, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov. 2017 Jul;7(7):675-693. doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.</citation>
    <PMID>28630051</PMID>
  </reference>
  <reference>
    <citation>Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.</citation>
    <PMID>25594173</PMID>
  </reference>
  <reference>
    <citation>Casanova JL, Abel L, Quintana-Murci L. Immunology taught by human genetics. Cold Spring Harb Symp Quant Biol. 2013;78:157-72. doi: 10.1101/sqb.2013.78.019968. Epub 2013 Oct 3.</citation>
    <PMID>24092470</PMID>
  </reference>
  <reference>
    <citation>Lucas CL, Lenardo MJ. Identifying genetic determinants of autoimmunity and immune dysregulation. Curr Opin Immunol. 2015 Dec;37:28-33. doi: 10.1016/j.coi.2015.09.001. Epub 2015 Oct 2.</citation>
    <PMID>26433354</PMID>
  </reference>
  <reference>
    <citation>Mak TW, Hakem A, McPherson JP, Shehabeldin A, Zablocki E, Migon E, Duncan GS, Bouchard D, Wakeham A, Cheung A, Karaskova J, Sarosi I, Squire J, Marth J, Hakem R. Brca1 required for T cell lineage development but not TCR loci rearrangement. Nat Immunol. 2000 Jul;1(1):77-82. doi: 10.1038/76950.</citation>
    <PMID>10881179</PMID>
  </reference>
  <reference>
    <citation>Cheung AM, Hande MP, Jalali F, Tsao MS, Skinnider B, Hirao A, McPherson JP, Karaskova J, Suzuki A, Wakeham A, You-Ten A, Elia A, Squire J, Bristow R, Hakem R, Mak TW. Loss of Brca2 and p53 synergistically promotes genomic instability and deregulation of T-cell apoptosis. Cancer Res. 2002 Nov 1;62(21):6194-204.</citation>
    <PMID>12414647</PMID>
  </reference>
  <reference>
    <citation>Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.</citation>
    <PMID>20798667</PMID>
  </reference>
  <reference>
    <citation>Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J Immunol. 2014 Oct 1;193(7):3528-37. doi: 10.4049/jimmunol.1302503. Epub 2014 Aug 29.</citation>
    <PMID>25172499</PMID>
  </reference>
  <reference>
    <citation>Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000 Dec 4;192(11):1553-62. doi: 10.1084/jem.192.11.1553.</citation>
    <PMID>11104798</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT04499534
org study id: UPCC 11119
secondary id: 834194
nct id: NCT04499534
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To evaluate immune function in BRCA1/2 mutation carriers without cancer, specifically to
      determine whether immune function in healthy individuals with germline loss of function
      BRCA1/2 mutations, impacts overall immune health and fitness.
observational model: Cohort
time perspective: Prospective
measure: To evaluate immune function in female BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination
time frame: 2 years
description: Analysis of the primary objective will depend on determination of the strain-specific neutralizing antibody titer change from day 0 to the last study visit, performed as the standard assay as described by the World Health Organization (WHO).
measure: Exploratory analysis- phenotypic evaluation of B cell
time frame: 2 years
description: Phenotypic evaluation of B and T cell responses to vaccine at each timepoint. Phenotypic analysis involves flow cytometry on peripheral blood mononuclear cells (PBMC) from all subjects (10 mL blood per subject).
measure: Exploratory analysis - transcriptional evaluation
time frame: 2 years
description: Transcriptional evaluation of B and T cell responses to vaccine on day 7-10 timepoint. Transcriptional analyses including quantitative real-time PCR (RT-qPCR) and RNA sequencing (RNAseq) may be performed on a subset of the study subjects on the day 7-10 time point.
intervention type: Biological
intervention name: Seasonal influenza vaccine
description: To evaluate immune function in BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 25 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Susan Domchek, MD
role: Principal Investigator
affiliation: University of Pennsylvania
last name: Susan Domchek, MD
phone: 215-615-3360
email: susan.domchek@pennmedicine.upenn.edu
last name: Heather Symecko, MPH
phone: 215-662-2770
email: hsymecko@pennmedicine.upenn.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
citation: Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov. 2017 Jul;7(7):675-693. doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.
PMID: 28630051
citation: Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.
PMID: 25594173
citation: Casanova JL, Abel L, Quintana-Murci L. Immunology taught by human genetics. Cold Spring Harb Symp Quant Biol. 2013;78:157-72. doi: 10.1101/sqb.2013.78.019968. Epub 2013 Oct 3.
PMID: 24092470
citation: Lucas CL, Lenardo MJ. Identifying genetic determinants of autoimmunity and immune dysregulation. Curr Opin Immunol. 2015 Dec;37:28-33. doi: 10.1016/j.coi.2015.09.001. Epub 2015 Oct 2.
PMID: 26433354
citation: Mak TW, Hakem A, McPherson JP, Shehabeldin A, Zablocki E, Migon E, Duncan GS, Bouchard D, Wakeham A, Cheung A, Karaskova J, Sarosi I, Squire J, Marth J, Hakem R. Brca1 required for T cell lineage development but not TCR loci rearrangement. Nat Immunol. 2000 Jul;1(1):77-82. doi: 10.1038/76950.
PMID: 10881179
citation: Cheung AM, Hande MP, Jalali F, Tsao MS, Skinnider B, Hirao A, McPherson JP, Karaskova J, Suzuki A, Wakeham A, You-Ten A, Elia A, Squire J, Bristow R, Hakem R, Mak TW. Loss of Brca2 and p53 synergistically promotes genomic instability and deregulation of T-cell apoptosis. Cancer Res. 2002 Nov 1;62(21):6194-204.
PMID: 12414647
citation: Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.
PMID: 20798667
citation: Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J Immunol. 2014 Oct 1;193(7):3528-37. doi: 10.4049/jimmunol.1302503. Epub 2014 Aug 29.
PMID: 25172499
citation: Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000 Dec 4;192(11):1553-62. doi: 10.1084/jem.192.11.1553.
PMID: 11104798
responsible party type: Sponsor
sharing ipd: No