<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/NCT03771157</url>
  </required_header>
  <id_info>
    <org_study_id>00003112</org_study_id>
    <nct_id>NCT03771157</nct_id>
  </id_info>
  <brief_title>Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors</brief_title>
  <official_title>Serologic Response to a New Recombinant, Adjuvanted Herpes Zoster Vaccine in Patients With Chronic Lymphocytic Leukemia and Waldenström Macroglobulinemia Treated With First-Line BTK Inhibitors - A Pilot Study</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to assess the capability of a patient with Chronic&#xD;
      Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) to generate an immune&#xD;
      response to the Shingrix vaccine under first-line BTK inhibitors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM) are known risk&#xD;
      factors for zoster reactivation, commonly called shingles. Although a recently FDA-approved&#xD;
      recombinant, adjuvanted herpes zoster vaccine (Shingrix) is currently being offered to these&#xD;
      populations, no study has specifically evaluated them.&#xD;
&#xD;
      The purpose of the study is to complete a single-arm trial evaluating if patients with CLL or&#xD;
      WM, while on treatment with first-line BTK inhibitors, can achieve immunologic response to&#xD;
      Shingrix. If effective, this will result in a new, well-tolerated shingles prevention&#xD;
      strategy for these patients.&#xD;
&#xD;
      The primary objective is to assess the capability to mount a humoral immune response to&#xD;
      Shingrix in patients with CLL or WM under first-line BTK inhibitors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">August 3, 2022</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>Early Phase 1</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A four-fold increase from baseline in serum immunoglobulin geometric mean titer to the gE viral antigen determined by enzyme linked immunosorbent assay (ELISA) at 4 weeks after vaccination.</measure>
    <time_frame>4 weeks following vaccination</time_frame>
    <description>Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with humoral immunity at 4 weeks after vaccination</measure>
    <time_frame>4 weeks following vaccination</time_frame>
    <description>Blood draws performed to measure persistence of measurable anti-gE and cellular-mediated immunity; cellular-mediated response will be determined by measuring PMBC activation (by ELISPOT or flow cytometry) following stimulation with varicella glycoprotein E peptide. PBMC activation at 4 weeks and 1 year post dose will be compared to pre-vaccination activation levels.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>A four-fold increase from baseline in serum immunoglobulin geometric mean titer to the gE viral antigen determined by enzyme linked immunosorbent assay (ELISA) at 2 years after vaccination.</measure>
    <time_frame>2 years following vaccination</time_frame>
    <description>Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of patients with humoral immunity at 2 years after vaccination</measure>
    <time_frame>2 years following vaccination</time_frame>
    <description>Blood draws performed to measure persistence of measurable anti-gE and cellular-mediated immunity; cellular-mediated response will be determined by measuring PMBC activation (by ELISPOT or flow cytometry) following stimulation with varicella glycoprotein E peptide. PBMC activation at 4 weeks and 2 years post dose will be compared to pre-vaccination activation levels.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Chronic Lymphocytic Leukemia (CLL)</condition>
  <condition>Waldenstrom Macroglobulinemia (WM)</condition>
  <arm_group>
    <arm_group_label>Shingrix shingles vaccine treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Shingrix vaccine</intervention_name>
    <description>On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.</description>
    <arm_group_label>Shingrix shingles vaccine treatment</arm_group_label>
    <other_name>Herpes Zoster Vaccine Recombinant, Adjuvanted</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  They are at least 50 years of age;&#xD;
&#xD;
          -  Have been diagnosed with chronic lymphocytic leukemia (CLL) OR Waldenström's&#xD;
             macroglobulinemia (WM)&#xD;
&#xD;
          -  Have been on first-line BTK inhibitor (ie ibrutinib or acalabrutinib) for at least 3&#xD;
             months,&#xD;
&#xD;
          -  Prior treatment with single agent rituximab is permitted if last dose was administered&#xD;
             over one year ago;&#xD;
&#xD;
          -  Have at least a one-year life expectancy;&#xD;
&#xD;
          -  Have a history of varicella (chicken-pox) OR lived in the US or any endemic country&#xD;
             for &gt; 30 years.&#xD;
&#xD;
          -  Prior radiation therapy is allowed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  They have a known hypersensitivity to a vaccine component;&#xD;
&#xD;
          -  Had herpes zoster reactivation within the past year;&#xD;
&#xD;
          -  Had received or were scheduled to receive a live virus vaccine in the period from 4&#xD;
             weeks prior to Dose 1 through 28 days post-second dose;&#xD;
&#xD;
          -  Had received or were scheduled to receive an inactivated vaccine in the period ranging&#xD;
             from 7 days prior to Dose 1 through 7 days post- second dose;&#xD;
&#xD;
          -  Are unable to give informed consent;&#xD;
&#xD;
          -  Have absolute lymphocyte counts greater than 20,000 X 109/L;&#xD;
&#xD;
          -  Are receiving treatment for CLL or WM with an additional agent other than a BTK&#xD;
             inhibitor;&#xD;
&#xD;
          -  Had rituximab treatment within a year prior to study start;&#xD;
&#xD;
          -  Had prior chemotherapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Friedberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Jonathan Friedberg</investigator_full_name>
    <investigator_title>Director of the Wilmot Cancer Institute</investigator_title>
  </responsible_party>
  <keyword>shingles vaccine (Shingrix)</keyword>
  <keyword>Chronic lymphocytic leukemia (CLL)</keyword>
  <keyword>Waldenstrom macroglobulinemia (WM)</keyword>
  <keyword>Pilot Study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03771157/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>April 24, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03771157
org study id: 00003112
nct id: NCT03771157
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary objective of the study is to assess the capability of a patient with Chronic
      Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) to generate an immune
      response to the Shingrix vaccine under first-line BTK inhibitors.
Chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM) are known risk
      factors for zoster reactivation, commonly called shingles. Although a recently FDA-approved
      recombinant, adjuvanted herpes zoster vaccine (Shingrix) is currently being offered to these
      populations, no study has specifically evaluated them.

      The purpose of the study is to complete a single-arm trial evaluating if patients with CLL or
      WM, while on treatment with first-line BTK inhibitors, can achieve immunologic response to
      Shingrix. If effective, this will result in a new, well-tolerated shingles prevention
      strategy for these patients.

      The primary objective is to assess the capability to mount a humoral immune response to
      Shingrix in patients with CLL or WM under first-line BTK inhibitors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: A four-fold increase from baseline in serum immunoglobulin geometric mean titer to the gE viral antigen determined by enzyme linked immunosorbent assay (ELISA) at 4 weeks after vaccination.
time frame: 4 weeks following vaccination
description: Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects
measure: Proportion of patients with humoral immunity at 4 weeks after vaccination
time frame: 4 weeks following vaccination
description: Blood draws performed to measure persistence of measurable anti-gE and cellular-mediated immunity; cellular-mediated response will be determined by measuring PMBC activation (by ELISPOT or flow cytometry) following stimulation with varicella glycoprotein E peptide. PBMC activation at 4 weeks and 1 year post dose will be compared to pre-vaccination activation levels.
measure: A four-fold increase from baseline in serum immunoglobulin geometric mean titer to the gE viral antigen determined by enzyme linked immunosorbent assay (ELISA) at 2 years after vaccination.
time frame: 2 years following vaccination
description: Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects
measure: Proportion of patients with humoral immunity at 2 years after vaccination
time frame: 2 years following vaccination
description: Blood draws performed to measure persistence of measurable anti-gE and cellular-mediated immunity; cellular-mediated response will be determined by measuring PMBC activation (by ELISPOT or flow cytometry) following stimulation with varicella glycoprotein E peptide. PBMC activation at 4 weeks and 2 years post dose will be compared to pre-vaccination activation levels.
arm group label: Shingrix shingles vaccine treatment
arm group type: Experimental
description: On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.
intervention type: Drug
intervention name: Shingrix vaccine
description: On day one, patients will receive the first of two doses of the Shingrix vaccine will be administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.
arm group label: Shingrix shingles vaccine treatment
other name: Herpes Zoster Vaccine Recombinant, Adjuvanted
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Jonathan Friedberg, MD
role: Principal Investigator
affiliation: University of Rochester
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Jonathan Friedberg
investigator title: Director of the Wilmot Cancer Institute
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Waldenstrom Macroglobulinemia
mesh term: Vaccines
provided document: 
submitted: April 24, 2023