<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/NCT04460235</url>
  </required_header>
  <id_info>
    <org_study_id>HEMATOVAC</org_study_id>
    <nct_id>NCT04460235</nct_id>
  </id_info>
  <brief_title>Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma</brief_title>
  <acronym>HEMATOVAC</acronym>
  <official_title>Immunogénicité de la Vaccination Anti-pneumococcique Dans la leucémie aiguë et le Lymphome Chez l'Adulte</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Poitiers University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Poitiers University Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</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 French Public Health Council recommended pneumococcal vaccination combined strategy for&#xD;
      all immunocompromised patients in 2012. This strategy consisted in conjugated 13-valent&#xD;
      pneumococcal injection followed 2 months later by polysaccharide 23-valent vaccine injection.&#xD;
      General practitioners are usually in charge of this vaccination. Conjugated pneumococcal&#xD;
      vaccine enhances the immunogenicity of the polysaccharide vaccine. Acute leukemia and&#xD;
      lymphoma are treated with multiple courses of chemotherapy, impairing the immune system and&#xD;
      potentially the response to vaccination. These patients are more at risk for developing&#xD;
      pneumococcal invasive diseases than the general population. However, efficacy of pneumococcal&#xD;
      vaccination is poorly documented in this setting. We assume that 70% of the patients are&#xD;
      non-responders to vaccination, according to their anti-pneumococcal immunoglobulin G titers&#xD;
      and the opsonophagocytic activity. To assess the immunogenicity of the pneumococcal&#xD;
      vaccination combined strategy in adult population of acute leukemia and lymphoma, the&#xD;
      investigator will measure anti-pneumococcal serotype-specific immunoglobulin G titers and&#xD;
      opsonophagocytic activity at different time-points after completion of the combined vaccine&#xD;
      strategy. The primary objective is to assess the immunogenicity of pneumococcal vaccination&#xD;
      combined strategy at 3 months after the 13-valent pneumococcal injection (corresponding to 1&#xD;
      month after the end of the combined strategy) using immunoglobulin G titers and&#xD;
      opsonophagocytic activity. At different time points (day 0, 1 month after the 13-valent&#xD;
      pneumococcal injection, the day of the injection of the polysaccharide 23-valent vaccine, one&#xD;
      month after the injection of the polysaccharide 23-valent vaccine, 3-6 months after the&#xD;
      polysaccharide 23-valent vaccine,9-12 months after the polysaccharide 23-valent vaccine), the&#xD;
      immunological response to vaccination will be monitored using specific-serotype&#xD;
      immunoglobulin G titers, opsonophagocytic activity, and total anti-pneumococcal&#xD;
      Immunoglobulin. The investigator will determine predictive factors of non-response to&#xD;
      vaccination by comparing demographic data, biological data and treatment received by both&#xD;
      acute myeloblastic leukemia and lymphoma patients. The tolerance and safety of the&#xD;
      vaccination strategy will also be assessed in this specific hematological population.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 9, 2021</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients having a good response to combined strategy</measure>
    <time_frame>39 months</time_frame>
    <description>Proportion of patients having a good response to combined strategy at 4 weeks after the end of the combined strategy. A good response to vaccination is defined by 4/7 tested serotypes responding to these 4 criteria: a serotype-specific immunoglobulin G titer ≥ 1μg/L (WHO threshold), a two-fold increase of this immunoglobulin G titer compare to baseline before vaccination, a serotype-specific opsonophagocytic activity ≥1/8, and a four-fold increase of functional antibodies compare to baseline.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Vaccine</condition>
  <condition>Streptococcus Pneumoniae</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Lymphoma, Non-Hodgkin</condition>
  <arm_group>
    <arm_group_label>Vaccination</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients will be vaccinated according to national guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prevenar13 Pneumo-23</intervention_name>
    <description>Vaccination according national guidelines</description>
    <arm_group_label>Vaccination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient ≥ 18 year-old.&#xD;
&#xD;
          -  AND medical follow-up in hematology unit&#xD;
&#xD;
          -  AND had received a first course of chemotherapy except demethylating for acute&#xD;
             myeloblastic leukemia without ProMyelogenousLeukemia-RetinoicAcidReceptor alpha and no&#xD;
             planned allogeneic hematopoietic stem cell transplantation (anti-IDH treatment&#xD;
             authorized) or for diffuse large B cell lymphoma or for follicular lymphoma&#xD;
&#xD;
          -  Life expectancy &gt; 6 months&#xD;
&#xD;
          -  Having signed the consent form&#xD;
&#xD;
          -  Having an health insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving monoclonal antibodies or biotherapies altering the immune response, other&#xD;
             than anti-Cluster of differentiation number 20 antibodies in the chemotherapy&#xD;
             protocol.&#xD;
&#xD;
          -  Uncontrolled bacterial, viral or fungal infection less than 7 days&#xD;
&#xD;
          -  Previous vaccination with 13-valent pneumococcal vaccine or polysaccharide 23-valent&#xD;
             vaccine (unless 13-valent pneumococcal vaccine was administered in childhood. The last&#xD;
             injection must be performed at least five years ago)&#xD;
&#xD;
          -  Preexisting condition that altered the immune response: splenectomy, HIV, primary or&#xD;
             secondary immune deficiency, nephrotic syndrome, sickle cell anemia, autoimmune&#xD;
             disorder, solid organ transplantation, immunosuppressive drugs or biotherapy not&#xD;
             included in the chemotherapy&#xD;
&#xD;
          -  Patient who already received chemotherapy for malignancy in the previous 2 years&#xD;
             before the inclusion&#xD;
&#xD;
          -  Allogeneic hematopoietic stem cell transplantation planned in the following 3 months&#xD;
             after the first chemotherapy course&#xD;
&#xD;
          -  Major blood clotting disorders preventing intramuscular injection&#xD;
&#xD;
          -  Medical history of anaphylactic reaction to vaccination&#xD;
&#xD;
          -  Known allergy to one of the vaccine components&#xD;
&#xD;
          -  Involvement to another vaccine biomedical research&#xD;
&#xD;
          -  Protected person&#xD;
&#xD;
          -  Pregnant women or women of childbearing age without appropriate contraceptive measures&#xD;
&#xD;
          -  Perfusion of polyvalent immunoglobulins during follow-up&#xD;
&#xD;
          -  Participants with hypersensitivity to aluminum phosphate, phenol or CRM197 protein,&#xD;
             protein derived from Corynebacterium diphtheria.&#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_contact>
    <last_name>Mathieu Puyade, MD, PhD</last_name>
    <phone>0033 5 49 44 32 76</phone>
    <email>mathieu.puyade@chu-poitiers.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Fanny Abriat</last_name>
    <phone>0033 5 49 44 37 96</phone>
    <email>fanny.abriat@chu-poitiers.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chu Angers</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mathilde HUNAULT, Pr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François-Xavier GROS, Dr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arnaud JACCARD, Pr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chu Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre PETERLIN, Dr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Pilar GALLEGO HERNANZ, Dr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ch Perigueux</name>
      <address>
        <city>Périgueux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claire CALMETTES, Dr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine MACHET, Dr</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 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>Pneumonia, Pneumococcal</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heptavalent Pneumococcal Conjugate Vaccine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT04460235
org study id: HEMATOVAC
nct id: NCT04460235
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
The French Public Health Council recommended pneumococcal vaccination combined strategy for
      all immunocompromised patients in 2012. This strategy consisted in conjugated 13-valent
      pneumococcal injection followed 2 months later by polysaccharide 23-valent vaccine injection.
      General practitioners are usually in charge of this vaccination. Conjugated pneumococcal
      vaccine enhances the immunogenicity of the polysaccharide vaccine. Acute leukemia and
      lymphoma are treated with multiple courses of chemotherapy, impairing the immune system and
      potentially the response to vaccination. These patients are more at risk for developing
      pneumococcal invasive diseases than the general population. However, efficacy of pneumococcal
      vaccination is poorly documented in this setting. We assume that 70% of the patients are
      non-responders to vaccination, according to their anti-pneumococcal immunoglobulin G titers
      and the opsonophagocytic activity. To assess the immunogenicity of the pneumococcal
      vaccination combined strategy in adult population of acute leukemia and lymphoma, the
      investigator will measure anti-pneumococcal serotype-specific immunoglobulin G titers and
      opsonophagocytic activity at different time-points after completion of the combined vaccine
      strategy. The primary objective is to assess the immunogenicity of pneumococcal vaccination
      combined strategy at 3 months after the 13-valent pneumococcal injection (corresponding to 1
      month after the end of the combined strategy) using immunoglobulin G titers and
      opsonophagocytic activity. At different time points (day 0, 1 month after the 13-valent
      pneumococcal injection, the day of the injection of the polysaccharide 23-valent vaccine, one
      month after the injection of the polysaccharide 23-valent vaccine, 3-6 months after the
      polysaccharide 23-valent vaccine,9-12 months after the polysaccharide 23-valent vaccine), the
      immunological response to vaccination will be monitored using specific-serotype
      immunoglobulin G titers, opsonophagocytic activity, and total anti-pneumococcal
      Immunoglobulin. The investigator will determine predictive factors of non-response to
      vaccination by comparing demographic data, biological data and treatment received by both
      acute myeloblastic leukemia and lymphoma patients. The tolerance and safety of the
      vaccination strategy will also be assessed in this specific hematological population.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients having a good response to combined strategy
time frame: 39 months
description: Proportion of patients having a good response to combined strategy at 4 weeks after the end of the combined strategy. A good response to vaccination is defined by 4/7 tested serotypes responding to these 4 criteria: a serotype-specific immunoglobulin G titer ≥ 1μg/L (WHO threshold), a two-fold increase of this immunoglobulin G titer compare to baseline before vaccination, a serotype-specific opsonophagocytic activity ≥1/8, and a four-fold increase of functional antibodies compare to baseline.
arm group label: Vaccination
arm group type: Other
description: All patients will be vaccinated according to national guidelines
intervention type: Drug
intervention name: Prevenar13 Pneumo-23
description: Vaccination according national guidelines
arm group label: Vaccination
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mathieu Puyade, MD, PhD
phone: 0033 5 49 44 32 76
email: mathieu.puyade@chu-poitiers.fr
last name: Fanny Abriat
phone: 0033 5 49 44 37 96
email: fanny.abriat@chu-poitiers.fr
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Pneumonia, Pneumococcal
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Non-Hodgkin
mesh term: Heptavalent Pneumococcal Conjugate Vaccine
sharing ipd: Undecided
ipd description: Undecided