<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/NCT04410900</url>
  </required_header>
  <id_info>
    <org_study_id>RG1007238</org_study_id>
    <secondary_id>NCI-2020-03444</secondary_id>
    <secondary_id>10411</secondary_id>
    <nct_id>NCT04410900</nct_id>
  </id_info>
  <brief_title>Vaccine Responsiveness After CAR-T Cell Therapy</brief_title>
  <official_title>Rabies Vaccination to Assess Vaccine Responsiveness After B Cell Targeted CAR-T Cell Therapies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fred Hutchinson Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial will use the inactivated rabies virus vaccine to assess immune function in&#xD;
      patients who previously underwent B cell targeted chimeric antigen receptor-modified T cell&#xD;
      immunotherapy (CARTx). A cohort of healthy volunteers will also be enrolled as a comparator&#xD;
      group. CARTx is a new treatment for patients with B-cell malignancies (cancer of the&#xD;
      B-cells), and the long-term effects of CARTx on immune function are not yet well understood.&#xD;
      Learning more about vaccine responsiveness in patients who previously underwent CARTx may&#xD;
      help doctors better understand immune function. The findings will guide evidence-based&#xD;
      strategies for infection prevention to improve outcomes in this rapidly growing population of&#xD;
      high-risk individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      Patients receive the inactivated rabies vaccine intramuscularly (IM) on day 1 and 6-10 weeks&#xD;
      later. Patients also undergo a blood collection prior to each vaccine, and at approximately&#xD;
      1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the&#xD;
      first immunization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Anticipated">February 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants with positive vaccine response</measure>
    <time_frame>4 weeks after the secondary vaccination</time_frame>
    <description>This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at week 4 post-secondary immunization. This RVNA titer is considered to be evidence of an adequate immune response by the World Health Organization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with sustained vaccine response</measure>
    <time_frame>6 months after the primary vaccination</time_frame>
    <description>This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at 6 months following the primary vaccination in participants who also receive secondary vaccination per-protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Longitudinal rabies virus neutralizing antibody (RVNA) titers</measure>
    <time_frame>From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.</time_frame>
    <description>Will compare quantitative levels of RVNA (log10 IU/mL) between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Longitudinal rabies virus binding IgM antibody titers</measure>
    <time_frame>From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.</time_frame>
    <description>Will compare quantitative levels of anti-rabies virus IgM between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Longitudinal rabies virus binding IgG antibody titers</measure>
    <time_frame>From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.</time_frame>
    <description>Will compare quantitative levels of anti-rabies virus IgG between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">41</enrollment>
  <condition>B-Cell Neoplasm</condition>
  <arm_group>
    <arm_group_label>Experimental (anti-rabies vaccine, collection of blood)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control (anti-rabies vaccine, collection of blood)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Wistar Rabies Virus Strain PM-1503-3M Vaccine</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Control (anti-rabies vaccine, collection of blood)</arm_group_label>
    <arm_group_label>Experimental (anti-rabies vaccine, collection of blood)</arm_group_label>
    <other_name>Imovax Rabies</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of blood samples</description>
    <arm_group_label>Control (anti-rabies vaccine, collection of blood)</arm_group_label>
    <arm_group_label>Experimental (anti-rabies vaccine, collection of blood)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients must be capable of understanding and providing a written&#xD;
             informed consent&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients must be 18 years of age or older, of any gender, race or&#xD;
             ethnicity&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients must have had relapse-free survival for &gt;= 6 months after&#xD;
             receiving CARTx for B-cell malignancies&#xD;
&#xD;
          -  CARTx RECIPIENTS: Platelet count &gt; 30,000 / mm^3&#xD;
&#xD;
          -  HEALTHY CONTROLS: Patients must be capable of understanding and providing a written&#xD;
             informed consent&#xD;
&#xD;
          -  HEALTHY CONTROLS: Patients must be 18 years of age or older, of any gender, race or&#xD;
             ethnicity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients who have received a hematopoietic cell transplant after&#xD;
             CARTx&#xD;
&#xD;
          -  CARTx RECIPIENTS: Previously received 1 or more rabies vaccines prior to the first&#xD;
             vaccine visit&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients who have received lymphodepleting therapies after CARTx and&#xD;
             within the past 6 months&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients with signs or symptoms of active infection&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients who are pregnant or breastfeeding&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients with previous known allergies to any component of the&#xD;
             vaccine&#xD;
&#xD;
          -  CARTx RECIPIENTS: Patients who have previously experienced a reaction to any vaccine&#xD;
             that required medical attention&#xD;
&#xD;
          -  CARTx RECIPIENTS: Study participants who report a severe adverse event following the&#xD;
             first rabies vaccine will not be eligible for a second dose&#xD;
&#xD;
          -  CARTx RECIPIENTS: Receiving corticosteroids &gt; 0.5 mg/kg/day prednisone equivalence in&#xD;
             the 7 days prior to first or second vaccination&#xD;
&#xD;
          -  HEALTHY CONTROLS: Previously received 1 or more rabies vaccines&#xD;
&#xD;
          -  HEALTHY CONTROLS: Chronic illness&#xD;
&#xD;
          -  HEALTHY CONTROLS: Signs or symptoms of active infection&#xD;
&#xD;
          -  HEALTHY CONTROLS: Pregnant or breastfeeding&#xD;
&#xD;
          -  HEALTHY CONTROLS: Patients with previous known allergies to any component of the&#xD;
             vaccine&#xD;
&#xD;
          -  HEALTHY CONTROLS: Previous reaction to a vaccine that required medical attention&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joshua A. Hill</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joshua A. Hill</last_name>
    <phone>206-667-6504</phone>
    <email>jahill3@fredhutch.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua A. Hill</last_name>
      <phone>206-667-6504</phone>
      <email>jahill3@fredhutch.org</email>
    </contact>
    <investigator>
      <last_name>Joshua A. Hill</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CAR T cells</keyword>
  <keyword>infection</keyword>
  <keyword>vaccine</keyword>
  <keyword>immunity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in a future article will be shared, after deidentification (text, tables, figures, and appendices).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will be shared beginning 3 months and ending 5 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared to achieve aims in the approved proposal. Proposals should be directed to Joshua A. Hill. To gain access, data requestors will need to sign a data access agreement.</ipd_access_criteria>
  </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/NCT04410900
org study id: RG1007238
secondary id: NCI-2020-03444
secondary id: 10411
nct id: NCT04410900
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial will use the inactivated rabies virus vaccine to assess immune function in
      patients who previously underwent B cell targeted chimeric antigen receptor-modified T cell
      immunotherapy (CARTx). A cohort of healthy volunteers will also be enrolled as a comparator
      group. CARTx is a new treatment for patients with B-cell malignancies (cancer of the
      B-cells), and the long-term effects of CARTx on immune function are not yet well understood.
      Learning more about vaccine responsiveness in patients who previously underwent CARTx may
      help doctors better understand immune function. The findings will guide evidence-based
      strategies for infection prevention to improve outcomes in this rapidly growing population of
      high-risk individuals.
OUTLINE:

      Patients receive the inactivated rabies vaccine intramuscularly (IM) on day 1 and 6-10 weeks
      later. Patients also undergo a blood collection prior to each vaccine, and at approximately
      1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the
      first immunization.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Proportion of participants with positive vaccine response
time frame: 4 weeks after the secondary vaccination
description: This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at week 4 post-secondary immunization. This RVNA titer is considered to be evidence of an adequate immune response by the World Health Organization.
measure: Proportion of participants with sustained vaccine response
time frame: 6 months after the primary vaccination
description: This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at 6 months following the primary vaccination in participants who also receive secondary vaccination per-protocol
measure: Longitudinal rabies virus neutralizing antibody (RVNA) titers
time frame: From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.
description: Will compare quantitative levels of RVNA (log10 IU/mL) between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.
measure: Longitudinal rabies virus binding IgM antibody titers
time frame: From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.
description: Will compare quantitative levels of anti-rabies virus IgM between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.
measure: Longitudinal rabies virus binding IgG antibody titers
time frame: From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.
description: Will compare quantitative levels of anti-rabies virus IgG between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.
arm group label: Experimental (anti-rabies vaccine, collection of blood)
arm group type: Experimental
description: Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.
arm group label: Control (anti-rabies vaccine, collection of blood)
arm group type: Active Comparator
description: Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.
intervention type: Biological
intervention name: Wistar Rabies Virus Strain PM-1503-3M Vaccine
description: Given IM
arm group label: Control (anti-rabies vaccine, collection of blood)
arm group label: Experimental (anti-rabies vaccine, collection of blood)
other name: Imovax Rabies
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo collection of blood samples
arm group label: Control (anti-rabies vaccine, collection of blood)
arm group label: Experimental (anti-rabies vaccine, collection of blood)
other name: Biological Sample Collection
other name: Biospecimen Collected
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Joshua A. Hill
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Joshua A. Hill
phone: 206-667-6504
email: jahill3@fredhutch.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma, B-Cell
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in a future article will be shared, after deidentification (text, tables, figures, and appendices).
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Analytic Code
ipd time frame: Data will be shared beginning 3 months and ending 5 years following article publication.
ipd access criteria: Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared to achieve aims in the approved proposal. Proposals should be directed to Joshua A. Hill. To gain access, data requestors will need to sign a data access agreement.