<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/NCT04484532</url>
  </required_header>
  <id_info>
    <org_study_id>I 54017</org_study_id>
    <secondary_id>NCI-2017-02157</secondary_id>
    <secondary_id>I 54017</secondary_id>
    <nct_id>NCT04484532</nct_id>
  </id_info>
  <brief_title>Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy and Healthy Volunteers</brief_title>
  <official_title>Evaluation of Antibody Response to High-Dose Seasonal Influenza Vaccination in Patients With Myeloid Malignancy Receiving Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roswell Park Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Roswell Park Cancer Institute</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot research trial studies the antibody response to high-dose seasonal influenza&#xD;
      vaccination in patients with myeloid malignancy receiving chemotherapy and healthy&#xD;
      volunteers. Evaluating antibody response to high-dose seasonal influenza vaccine may serve as&#xD;
      a basis for vaccine recommendations in patients with myeloid malignancies and provide&#xD;
      insights into the status of the immune system in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To investigate the antibody response to influenza vaccination in patients with acute&#xD;
      myeloid leukemia (AML) or myelodysplastic syndrome (MDS) receiving hypomethylating agents&#xD;
      (decitabine or azacytidine) compared to normal healthy controls and those patients with&#xD;
      similar disorders receiving cytarabine containing intensive chemotherapy or best supportive&#xD;
      care.&#xD;
&#xD;
      II. To collect and store blood samples at different time points (prior to and after&#xD;
      vaccination) for assessment of influenza specific T-cell subsets using tetramers by flow&#xD;
      cytometry.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine&#xD;
      intramuscularly (IM) on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time,&#xD;
      patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent&#xD;
      therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset&#xD;
      of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days&#xD;
      115-185.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 17, 2017</start_date>
  <completion_date type="Actual">June 7, 2022</completion_date>
  <primary_completion_date type="Actual">June 7, 2022</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>Antibody response (by microneutralization assay) to influenza vaccination</measure>
    <time_frame>Up to 4-6 months post-vaccination</time_frame>
    <description>The geometric mean (GMT) and standard deviation of antibody titers will be calculated by cohort at the baseline assessment and 1-3 months post vaccination time points. Antibody response is assessed using the outcome measures: seroprotection, seroconversion, and GMT. Seroprotection is defined as an hemagglutination inhibition (HAI) titer &gt;= 1:40 of each individual influenza antigen. Seroconversion is defined as &gt;= 4-fold increase in post-vaccination titer of each individual influenza antigen. The seroprotection and seroconversion rates will be reported by age strata, cohort, and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The GMT at each time-point will be compared using one-sided permutation T-tests about the log-transformed data. The GMT ratio (GMTR) between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>T-cell subset population assessed using flow cytometry</measure>
    <time_frame>Up to 4-6 months post-vaccination</time_frame>
    <description>T-cell subset populations will be correlated with antibody responses to influenza vaccination. Blood samples will be collected and stored at different time-points for assessment of T-cell response to influenza vaccination using influenza specific tetramer staining by flow cytometry. The seroprotection and seroconversion rates will be reported by cohort and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The rates will be compared between the lenalidomide and healthy control cohorts using one-sided Barnard's tests. The GMTR between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <arm_group>
    <arm_group_label>Supportive Care (trivalent influenza vaccine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine IM on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time, patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days 115-185.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Trivalent Influenza Vaccine</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Supportive Care (trivalent influenza vaccine)</arm_group_label>
    <other_name>Agriflu</other_name>
    <other_name>Flu prevention</other_name>
    <other_name>Flu prophylaxis</other_name>
    <other_name>Flu shot</other_name>
    <other_name>Flu vaccination</other_name>
    <other_name>Fluarix</other_name>
    <other_name>Flublok</other_name>
    <other_name>FluLaval</other_name>
    <other_name>Flushield</other_name>
    <other_name>Fluvirin</other_name>
    <other_name>Fluzone High-dose (HD)</other_name>
    <other_name>Influenza Vaccine</other_name>
    <other_name>Influenza Virus Vaccine, Trivalent, Types A and B</other_name>
    <other_name>Trivalent Influenza Vaccine (TIV)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject or legal representative must understand the investigational nature of this&#xD;
             study and sign an Independent Ethics Committee/Institutional Review Board approved&#xD;
             written informed consent form prior to undergoing any investigational biospecimen&#xD;
             (blood) collection procedure&#xD;
&#xD;
          -  Willing to undergo seasonal influenza vaccination with Fluzone high dose at Roswell&#xD;
             Park Cancer Institute within 2 weeks of enrollment of this study&#xD;
&#xD;
          -  Estimated survival of 8 weeks or more following enrollment on the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             influenza infection or influenza-like-illness&#xD;
&#xD;
          -  Women who are attempting pregnancy or known to be pregnant by clinical history or&#xD;
             nursing female subjects&#xD;
&#xD;
          -  Unwilling or unable to follow protocol requirements&#xD;
&#xD;
          -  Use of prednisone &gt; 10 mg/day (or its equivalent for other steroids) for &gt; 2 weeks&#xD;
             immediately prior to receiving seasonal influenza vaccination&#xD;
&#xD;
          -  Received dose of seasonal influenza vaccination prior to enrollment&#xD;
&#xD;
          -  Participation at the time of study enrollment in another clinical trial investigating&#xD;
             immunotherapeutic agents (like anti-PD1 or anti-PDL1 or anti-CTLA4 antibodies or&#xD;
             vaccines); concurrent participation in an observational/non-interventional study or an&#xD;
             interventional study investigating tyrosine kinase inhibitor or other targeted agents&#xD;
             use is acceptable&#xD;
&#xD;
          -  Inability to receive seasonal influenza vaccine due to prior hypersensitivity to eggs,&#xD;
             chicken proteins, or any of the vaccine components&#xD;
&#xD;
          -  History of a life-threatening reaction to influenza vaccination or to a vaccine&#xD;
             containing similar substances&#xD;
&#xD;
          -  Personal history of Guillain-Barre syndrome&#xD;
&#xD;
          -  Any condition which in the investigator's opinion deems the subject an unsuitable&#xD;
             candidate to receive annual influenza vaccination or may potentially affect the&#xD;
             response to influenza vaccination&#xD;
&#xD;
          -  Adults unable to consent, individuals who are not yet adults (infants, children, and&#xD;
             teenagers), women who are known to be pregnant, attempting pregnancy, or nursing&#xD;
             women, and prisoners will be excluded from the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth A Griffiths</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roswell Park Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>June 2, 2023</last_update_submitted>
  <last_update_submitted_qc>June 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 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>Myelodysplastic Syndromes</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/NCT04484532
org study id: I 54017
secondary id: NCI-2017-02157
secondary id: I 54017
nct id: NCT04484532
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This pilot research trial studies the antibody response to high-dose seasonal influenza
      vaccination in patients with myeloid malignancy receiving chemotherapy and healthy
      volunteers. Evaluating antibody response to high-dose seasonal influenza vaccine may serve as
      a basis for vaccine recommendations in patients with myeloid malignancies and provide
      insights into the status of the immune system in these patients.
PRIMARY OBJECTIVES:

      I. To investigate the antibody response to influenza vaccination in patients with acute
      myeloid leukemia (AML) or myelodysplastic syndrome (MDS) receiving hypomethylating agents
      (decitabine or azacytidine) compared to normal healthy controls and those patients with
      similar disorders receiving cytarabine containing intensive chemotherapy or best supportive
      care.

      II. To collect and store blood samples at different time points (prior to and after
      vaccination) for assessment of influenza specific T-cell subsets using tetramers by flow
      cytometry.

      OUTLINE:

      Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine
      intramuscularly (IM) on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time,
      patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent
      therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset
      of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days
      115-185.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Antibody response (by microneutralization assay) to influenza vaccination
time frame: Up to 4-6 months post-vaccination
description: The geometric mean (GMT) and standard deviation of antibody titers will be calculated by cohort at the baseline assessment and 1-3 months post vaccination time points. Antibody response is assessed using the outcome measures: seroprotection, seroconversion, and GMT. Seroprotection is defined as an hemagglutination inhibition (HAI) titer >= 1:40 of each individual influenza antigen. Seroconversion is defined as >= 4-fold increase in post-vaccination titer of each individual influenza antigen. The seroprotection and seroconversion rates will be reported by age strata, cohort, and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The GMT at each time-point will be compared using one-sided permutation T-tests about the log-transformed data. The GMT ratio (GMTR) between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
measure: T-cell subset population assessed using flow cytometry
time frame: Up to 4-6 months post-vaccination
description: T-cell subset populations will be correlated with antibody responses to influenza vaccination. Blood samples will be collected and stored at different time-points for assessment of T-cell response to influenza vaccination using influenza specific tetramer staining by flow cytometry. The seroprotection and seroconversion rates will be reported by cohort and time-point (1-3 months and 4-6 months post vaccination) using 95% confidence intervals obtained using Jeffrey's prior method. The rates will be compared between the lenalidomide and healthy control cohorts using one-sided Barnard's tests. The GMTR between 1-3 months post vaccination and baseline will also be calculated and reported by cohort using a 95% confidence interval.
arm group label: Supportive Care (trivalent influenza vaccine)
arm group type: Experimental
description: Within 14 days of baseline influenza titer, patients receive trivalent influenza vaccine IM on day 0 (patients in cohorts 1 and 5 receive the vaccine at any time, patients in cohorts 2 and 3 receive the vaccine between days 14-25 of hypomethylating agent therapy course, and patients in cohort 4 receive the vaccine between days 21-365 from onset of cytotoxic chemotherapy). Patients then undergo titer assessment at days 25-90 and days 115-185.
intervention type: Biological
intervention name: Trivalent Influenza Vaccine
description: Given IM
arm group label: Supportive Care (trivalent influenza vaccine)
other name: Agriflu
other name: Flu prevention
other name: Flu prophylaxis
other name: Flu shot
other name: Flu vaccination
other name: Fluarix
other name: Flublok
other name: FluLaval
other name: Flushield
other name: Fluvirin
other name: Fluzone High-dose (HD)
other name: Influenza Vaccine
other name: Influenza Virus Vaccine, Trivalent, Types A and B
other name: Trivalent Influenza Vaccine (TIV)
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Elizabeth A Griffiths
role: Principal Investigator
affiliation: Roswell Park Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Myelodysplastic Syndromes
mesh term: Vaccines