<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/NCT03023631</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0714</org_study_id>
    <secondary_id>NCI-2018-02606</secondary_id>
    <secondary_id>2016-0714</secondary_id>
    <nct_id>NCT03023631</nct_id>
  </id_info>
  <brief_title>Gardasil 9 Vaccine in Preventing HPV Infection in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant</brief_title>
  <official_title>Human Papillomavirus Antibody Response After GARDASIL 9 Vaccination in Patients After Allogeneic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase IV trial studies how well Gardasil 9 vaccine works in preventing human&#xD;
      papillomavirus (HPV) infection in patients with hematologic malignancies who are undergoing&#xD;
      donor stem cell transplant. Vaccines, such as Gardasil 9, may help the body build an&#xD;
      effective immune response to kill cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the immunogenicity of recombinant human papillomavirus nonavalent vaccine&#xD;
      (GARDASIL 9) administered after allogeneic stem cell transplant (SCT) in patients with&#xD;
      hematologic malignancy by comparing HPV 9-plex competitive Luminex immunoassay (9-plex cLIA)&#xD;
      titers before and after GARDASIL 9 administration.&#xD;
&#xD;
      II. To evaluate the safety and tolerability of GARDASIL 9 administered after allogeneic SCT&#xD;
      in patients with hematologic malignancy.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following&#xD;
      transplant, patients receive recombinant human papillomavirus nonavalent vaccine&#xD;
      intramuscularly (IM) on day 0 and at 2 and 6 months in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study intervention, patients are followed up within 3 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 23, 2017</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Antibody response defined as numerically elevated antibody titer of any type at 1 month post-dose 3 (month 7)</measure>
    <time_frame>At 1 month post-dose 3</time_frame>
    <description>Antibody response at 1 month post-dose 3 (month 7) will be compared with baseline antibody level. The study will use results from the 9-plex competitive Luminex immunoassay (9-plex cLIA) test to estimate the antibody response rate at dose 3 with 95% confidence interval (CI). Will apply Student t-test/Wilcoxon test to compare continuous variables between patients who obtained antibody response as defined in the primary endpoint (responders) and those who did not respond (non-responders), and the chi-square test or the Fisher's exact test to assess the association between response status and patients' demographic and clinical characteristics. Logistic regression analysis will be used to assess the multivariate relationship between patient demographic and clinical characteristics on the probability of antibody response.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</measure>
    <time_frame>Up to 3 days post-intervention</time_frame>
    <description>Safety and tolerability of recombinant human papillomavirus nonavalent vaccine measured by occurrence of grade &gt;= 3 adverse events (AEs) that are possibly, probably, or definitely related to recombinant human papillomavirus nonavalent vaccine for all 3 vaccine administrations. The study will report the AE rate with a corresponding upper bound of a 1-sided 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody persistence at 6 months post-dose 3</measure>
    <time_frame>At 6 months post-dose 3</time_frame>
    <description>Antibody persistence at 6 months post-dose 3 will be compared with 1 month post-dose 3. The study will apply a paired t-test with noninferiority hypotheses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Human papillomavirus (HPV) vaccination completion rate</measure>
    <time_frame>Up to 3 days post-intervention</time_frame>
    <description>The study will calculate the proportion of patients who are able to complete the 3 shot series of HPV vaccination. Will describe them in terms of demographics, and clinical characteristics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimation of antibody titers</measure>
    <time_frame>At 6-12 months post-transplant, and at 1 and 6 months post-dose 3</time_frame>
    <description>Antibody titer will be measured repeatedly by the 9-plex cLIA test. Appropriate transformation (e.g. log transformation) of antibody titer will be used in the analyses to satisfy the normality assumption of linear or linear mixed effect model. Geometric mean titers will be used to summarize antibody titer at each time point. Linear mixed effect models for repeated measures analysis will be employed to assess change in antibody titer over time and to compare antibody titer change over time between different patient groups adjusting for other important covariates including disease characteristics (tumor stage, site, pathology), and other patient prognostic factors. Interaction between time and patients' characteristics on the change of antibody titer will be also investigated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Allogeneic Hematopoietic Stem Cell Transplant Recipient</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <arm_group>
    <arm_group_label>Prevention (Gardasil 9 vaccine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following transplant, patients receive recombinant human papillomavirus nonavalent vaccine IM on day 0 and at 2 and 6 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant Human Papillomavirus Nonavalent Vaccine</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Prevention (Gardasil 9 vaccine)</arm_group_label>
    <other_name>Gardasil 9</other_name>
    <other_name>Nonavalent HPV VLP Vaccine</other_name>
    <other_name>Recombinant HPV Nonavalent Vaccine</other_name>
    <other_name>Recombinant Human Papillomavirus 9-valent Vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All English-speaking adult MD Anderson patients with hematologic malignancy at 6-12&#xD;
             months +/- 8 weeks post allogeneic stem cell transplantation who will receive usual&#xD;
             post-stem cell transplant vaccinations&#xD;
&#xD;
          -  All patients from approved protocol 2015-0795 will be invited to this vaccine study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior allogeneic SCT&#xD;
&#xD;
          -  Platelet count less than or equal to 25,000 K/uL&#xD;
&#xD;
          -  Absolute neutrophil count less than or equal to 500/uL&#xD;
&#xD;
          -  Patients who have ever received HPV vaccination (at least one dose of HPV vaccine)&#xD;
&#xD;
          -  Patients with a prior history of HPV-related malignancy&#xD;
&#xD;
          -  Female patients who tested positive for pregnancy during pre-SCT evaluation&#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>Jessica P Hwang</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</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>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03023631
org study id: 2016-0714
secondary id: NCI-2018-02606
secondary id: 2016-0714
nct id: NCT03023631
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase IV trial studies how well Gardasil 9 vaccine works in preventing human
      papillomavirus (HPV) infection in patients with hematologic malignancies who are undergoing
      donor stem cell transplant. Vaccines, such as Gardasil 9, may help the body build an
      effective immune response to kill cancer cells.
PRIMARY OBJECTIVES:

      I. To determine the immunogenicity of recombinant human papillomavirus nonavalent vaccine
      (GARDASIL 9) administered after allogeneic stem cell transplant (SCT) in patients with
      hematologic malignancy by comparing HPV 9-plex competitive Luminex immunoassay (9-plex cLIA)
      titers before and after GARDASIL 9 administration.

      II. To evaluate the safety and tolerability of GARDASIL 9 administered after allogeneic SCT
      in patients with hematologic malignancy.

      OUTLINE:

      Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following
      transplant, patients receive recombinant human papillomavirus nonavalent vaccine
      intramuscularly (IM) on day 0 and at 2 and 6 months in the absence of disease progression or
      unacceptable toxicity.

      After completion of study intervention, patients are followed up within 3 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Antibody response defined as numerically elevated antibody titer of any type at 1 month post-dose 3 (month 7)
time frame: At 1 month post-dose 3
description: Antibody response at 1 month post-dose 3 (month 7) will be compared with baseline antibody level. The study will use results from the 9-plex competitive Luminex immunoassay (9-plex cLIA) test to estimate the antibody response rate at dose 3 with 95% confidence interval (CI). Will apply Student t-test/Wilcoxon test to compare continuous variables between patients who obtained antibody response as defined in the primary endpoint (responders) and those who did not respond (non-responders), and the chi-square test or the Fisher's exact test to assess the association between response status and patients' demographic and clinical characteristics. Logistic regression analysis will be used to assess the multivariate relationship between patient demographic and clinical characteristics on the probability of antibody response.
measure: Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
time frame: Up to 3 days post-intervention
description: Safety and tolerability of recombinant human papillomavirus nonavalent vaccine measured by occurrence of grade >= 3 adverse events (AEs) that are possibly, probably, or definitely related to recombinant human papillomavirus nonavalent vaccine for all 3 vaccine administrations. The study will report the AE rate with a corresponding upper bound of a 1-sided 95% CI.
measure: Antibody persistence at 6 months post-dose 3
time frame: At 6 months post-dose 3
description: Antibody persistence at 6 months post-dose 3 will be compared with 1 month post-dose 3. The study will apply a paired t-test with noninferiority hypotheses.
measure: Human papillomavirus (HPV) vaccination completion rate
time frame: Up to 3 days post-intervention
description: The study will calculate the proportion of patients who are able to complete the 3 shot series of HPV vaccination. Will describe them in terms of demographics, and clinical characteristics.
measure: Estimation of antibody titers
time frame: At 6-12 months post-transplant, and at 1 and 6 months post-dose 3
description: Antibody titer will be measured repeatedly by the 9-plex cLIA test. Appropriate transformation (e.g. log transformation) of antibody titer will be used in the analyses to satisfy the normality assumption of linear or linear mixed effect model. Geometric mean titers will be used to summarize antibody titer at each time point. Linear mixed effect models for repeated measures analysis will be employed to assess change in antibody titer over time and to compare antibody titer change over time between different patient groups adjusting for other important covariates including disease characteristics (tumor stage, site, pathology), and other patient prognostic factors. Interaction between time and patients' characteristics on the change of antibody titer will be also investigated.
arm group label: Prevention (Gardasil 9 vaccine)
arm group type: Experimental
description: Patients undergo standard of care allogeneic stem cell transplant. 6-12 months following transplant, patients receive recombinant human papillomavirus nonavalent vaccine IM on day 0 and at 2 and 6 months in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Recombinant Human Papillomavirus Nonavalent Vaccine
description: Given IM
arm group label: Prevention (Gardasil 9 vaccine)
other name: Gardasil 9
other name: Nonavalent HPV VLP Vaccine
other name: Recombinant HPV Nonavalent Vaccine
other name: Recombinant Human Papillomavirus 9-valent Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jessica P Hwang
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Hematologic Neoplasms
mesh term: Vaccines