<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/NCT04415918</url>
  </required_header>
  <id_info>
    <org_study_id>20-432</org_study_id>
    <nct_id>NCT04415918</nct_id>
  </id_info>
  <brief_title>Bezlotoxumab Efficacy and Tolerability in Cancer Patient</brief_title>
  <official_title>Is Bezlotoxumab Effective, Tolerable and Cost Saving in Preventing Recurrent Clostridium Difficile Infections in Patients With Malignancies? An Exploratory Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cooper Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cooper Health System</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigation of efficacy and tolerability of bezlotoxumab in patients with cancer diagnosis&#xD;
      in terms of preventing CDI recurrence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be prospective, open-label, single center with historical control. All&#xD;
      procedures will be conducted according to Good Clinical Practice guidelines and the&#xD;
      provisions of the Declaration of Helsinki. Approval of Institutional Review Board at Cooper&#xD;
      Health Care will be obtained prior to commencing the study and actively enrolled patients&#xD;
      will sign an informed consent form. Data will be collected on a case report form and&#xD;
      confidentiality will be protected according to laws and regulations. Study population will&#xD;
      include adult cancer patients diagnosed with CDI being treated at MD Anderson cancer center&#xD;
      affiliated with Cooper University Hospital, Camden, NJ, USA. The comparison arm will be a&#xD;
      historical group of patients treated at the same center with same inclusion/exclusion&#xD;
      criteria within the previous 3 years of start date.&#xD;
&#xD;
      Recruited patients will receive a single dose of Bezlotoxumab (Zinplava) 10mg/kg (actual body&#xD;
      weight) 60-minute intravenous infusion during active CDI treatments.&#xD;
&#xD;
      For pharmacoeconomic analysis, data collected from the financial department will include&#xD;
      total hospitalization costs, drug costs, length of stay, total amount charged and total&#xD;
      amount reimbursedpertaining to CDI diagnosis code/ICD-10 for recurrent CDI. The analysis will&#xD;
      encompass the perspectives of the hospital and the third party payer. Adjustment of&#xD;
      retrospective cost data will be performed using Medical Consumer Price index (MCPI) inflation&#xD;
      rates established by Bureau of Labor Statistics. Cost-avoidance analysis will be performed to&#xD;
      determine the cost of preventing recurrence. Incremental cost-effectiveness ratio (ICER)&#xD;
      defined as the difference in cost divided by difference in outcomes will be reported. The&#xD;
      outcome being examined, the percent of recurrences avoided, will be used in the denominator.&#xD;
      Graphically, a cost-effectiveness plane will be used to depict the comparison. Secondary&#xD;
      analyses will examine specific differences between groups, including total drug costs, length&#xD;
      of stay (LOS) and per diem hospitalization costs. Univariate sensitivity analyses will be&#xD;
      conducted to determine robustness of the analysis.&#xD;
&#xD;
      Matching of intervention group with control will be based on inclusion/exclusion criteria,&#xD;
      sex, and GEIH-CDI propensity score as shown in the table below. Matching will be in the ratio&#xD;
      of 1:2. Selected historical control based on inclusion/exclusion criteria will matched to&#xD;
      same sex.&#xD;
&#xD;
      Patients treated at MD Anderson cancer center affiliated with Cooper University Hospital&#xD;
      Camden, NJ, USA with diagnosis of CDI will be screened using inclusion/exclusion criteria.&#xD;
      Eligible patients will be approached for consent. Recruited patients will receive the study&#xD;
      intervention either as in-patients or at the out-patient infusion unit according to their&#xD;
      current status. The study patients will be followed for 12 weeks (day1 is the day of study&#xD;
      intervention) on week1, week2, week 4, week 8 and week 12 (- or + 5 days) until study exit&#xD;
      day. Study required clinical data will be collected from medical records on case report form.&#xD;
      Financial data will be acquired from accounting department records. Recruited patients will&#xD;
      be interviewed on the phone or in person.&#xD;
&#xD;
      Study intervention drug will be stored at the Pharmacy Department, Cooper University&#xD;
      Hospital. Shortly before the time of administration, infusion will be prepared as per&#xD;
      manufacturer instructions (250 mL infused over 1 hours through 0.22-micron sterile filter&#xD;
      controlled by volumetric pump) and transported for administration per the hospital protocol.&#xD;
      Patients receiving bezolotoxumab infusion will be under observation and follow up as per&#xD;
      study protocol.&#xD;
&#xD;
      To assess recurrence, clinical cure is achieved in patients receiving standard of care&#xD;
      treatment and have no diarrhea (&lt; 3 bowel movements per day) for 2 consecutive days following&#xD;
      completion of therapy. Patients will be followed by reviewing medical records, in person and&#xD;
      by phone.&#xD;
&#xD;
      Tolerability of bezolotoxumab will be assessed by collecting clinical and laboratory data&#xD;
      about adverse events as detailed below under adverse experience reporting.&#xD;
&#xD;
      A 10-mL blood sample will be collected from patients in heparinized tubes (processed and/or&#xD;
      stored as required by the lab) for genetic DNA profiling. An an assessment of bezlotoxumab&#xD;
      efficacy and the correlation with the SNP will be performed.&#xD;
&#xD;
      Withdrawal from the study will be voluntary or at the discretion of investigators/sponsor in&#xD;
      case of tolerability concerns, protocol violation or any other reason.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of patients with recurrent CDIs within 12 weeks of initial cure compared with historical group of patients selected with same inclusion/exclusion criteria (same center within 3 years of the start date of the study).</measure>
    <time_frame>12 weeks</time_frame>
    <description>Documentation of recurrent CDI infection</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine if bezlotoxumab infusion add-on treatment is cost saving in patients with malignancies in terms of preventing CDI recurrence.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Pharmacoeconomic analysis</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Explore if genetic variants (SNP rs2516513 on xMHC, SNP genotype on IL-8 gene promotor, SNP rs2243250 IL-4 gene,….) are associated with increased recurrence of CDI in this patient population.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Genetic analysis is performed to describe gene type</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">132</enrollment>
  <condition>Clostridium Difficile Infection Recurrence</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recruited patient according inclusion/exclusion criteria</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Historical control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Cohort of historical patients matched to study population to serve as control</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bezlotoxumab Injection</intervention_name>
    <description>A single dose of Bezlotoxumab (Zinplava) 10mg/kg (actual body weight) 60-minute intravenous infusion during active CDI treatments.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>No intervention</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients &gt; 18 years of age&#xD;
&#xD;
          2. Diagnosed with any type of malignancy and receiving active treatment (chemotherapy,&#xD;
             radiotherapy or biological therapy)&#xD;
&#xD;
          3. Confirmed clinical (patients with unexplained and new-onset &gt;3 unformed stools in 24&#xD;
             hours) and laboratory (a stool toxin test as part of a multistep algorithm) diagnosis&#xD;
             of primary or recurrent CDI and receiving standard of care treatment&#xD;
&#xD;
          4. Patient or legally authorized person signs informed consent form -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1- Patients with short life expectancy including terminal cancer, multi-organ dysfunction&#xD;
        or on compassionate care (as per treating physician) 2- Pregnant or breastfeeding female&#xD;
        patients or likely to be pregnant without negative laboratory confirmation 3- Patients with&#xD;
        active chronic diarrheal disease 4- Patients with other acute, unstable and&#xD;
        life-threatening conditions (acute renal or hepatic failure, sepsis or other severe&#xD;
        infections, active bleeding, stroke or myocardial infarction) 5- Patient receiving or&#xD;
        planning to receive other CDI interventions like FMT within 3 months of bezlotuxumab&#xD;
        therapy 6- Patients who previously received bezlotoxumab within the past 3 months 7-&#xD;
        Patients completed active of CDI treatment 8- Patients with any conditions that at&#xD;
        discretion of the investigators will compromise patient rights, ability to participate or&#xD;
        complete the study&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</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>Infections</mesh_term>
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be shared</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/NCT04415918
org study id: 20-432
nct id: NCT04415918
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Investigation of efficacy and tolerability of bezlotoxumab in patients with cancer diagnosis
      in terms of preventing CDI recurrence.
The study will be prospective, open-label, single center with historical control. All
      procedures will be conducted according to Good Clinical Practice guidelines and the
      provisions of the Declaration of Helsinki. Approval of Institutional Review Board at Cooper
      Health Care will be obtained prior to commencing the study and actively enrolled patients
      will sign an informed consent form. Data will be collected on a case report form and
      confidentiality will be protected according to laws and regulations. Study population will
      include adult cancer patients diagnosed with CDI being treated at MD Anderson cancer center
      affiliated with Cooper University Hospital, Camden, NJ, USA. The comparison arm will be a
      historical group of patients treated at the same center with same inclusion/exclusion
      criteria within the previous 3 years of start date.

      Recruited patients will receive a single dose of Bezlotoxumab (Zinplava) 10mg/kg (actual body
      weight) 60-minute intravenous infusion during active CDI treatments.

      For pharmacoeconomic analysis, data collected from the financial department will include
      total hospitalization costs, drug costs, length of stay, total amount charged and total
      amount reimbursedpertaining to CDI diagnosis code/ICD-10 for recurrent CDI. The analysis will
      encompass the perspectives of the hospital and the third party payer. Adjustment of
      retrospective cost data will be performed using Medical Consumer Price index (MCPI) inflation
      rates established by Bureau of Labor Statistics. Cost-avoidance analysis will be performed to
      determine the cost of preventing recurrence. Incremental cost-effectiveness ratio (ICER)
      defined as the difference in cost divided by difference in outcomes will be reported. The
      outcome being examined, the percent of recurrences avoided, will be used in the denominator.
      Graphically, a cost-effectiveness plane will be used to depict the comparison. Secondary
      analyses will examine specific differences between groups, including total drug costs, length
      of stay (LOS) and per diem hospitalization costs. Univariate sensitivity analyses will be
      conducted to determine robustness of the analysis.

      Matching of intervention group with control will be based on inclusion/exclusion criteria,
      sex, and GEIH-CDI propensity score as shown in the table below. Matching will be in the ratio
      of 1:2. Selected historical control based on inclusion/exclusion criteria will matched to
      same sex.

      Patients treated at MD Anderson cancer center affiliated with Cooper University Hospital
      Camden, NJ, USA with diagnosis of CDI will be screened using inclusion/exclusion criteria.
      Eligible patients will be approached for consent. Recruited patients will receive the study
      intervention either as in-patients or at the out-patient infusion unit according to their
      current status. The study patients will be followed for 12 weeks (day1 is the day of study
      intervention) on week1, week2, week 4, week 8 and week 12 (- or + 5 days) until study exit
      day. Study required clinical data will be collected from medical records on case report form.
      Financial data will be acquired from accounting department records. Recruited patients will
      be interviewed on the phone or in person.

      Study intervention drug will be stored at the Pharmacy Department, Cooper University
      Hospital. Shortly before the time of administration, infusion will be prepared as per
      manufacturer instructions (250 mL infused over 1 hours through 0.22-micron sterile filter
      controlled by volumetric pump) and transported for administration per the hospital protocol.
      Patients receiving bezolotoxumab infusion will be under observation and follow up as per
      study protocol.

      To assess recurrence, clinical cure is achieved in patients receiving standard of care
      treatment and have no diarrhea (< 3 bowel movements per day) for 2 consecutive days following
      completion of therapy. Patients will be followed by reviewing medical records, in person and
      by phone.

      Tolerability of bezolotoxumab will be assessed by collecting clinical and laboratory data
      about adverse events as detailed below under adverse experience reporting.

      A 10-mL blood sample will be collected from patients in heparinized tubes (processed and/or
      stored as required by the lab) for genetic DNA profiling. An an assessment of bezlotoxumab
      efficacy and the correlation with the SNP will be performed.

      Withdrawal from the study will be voluntary or at the discretion of investigators/sponsor in
      case of tolerability concerns, protocol violation or any other reason.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The proportion of patients with recurrent CDIs within 12 weeks of initial cure compared with historical group of patients selected with same inclusion/exclusion criteria (same center within 3 years of the start date of the study).
time frame: 12 weeks
description: Documentation of recurrent CDI infection
measure: Determine if bezlotoxumab infusion add-on treatment is cost saving in patients with malignancies in terms of preventing CDI recurrence.
time frame: 12 weeks
description: Pharmacoeconomic analysis
measure: Explore if genetic variants (SNP rs2516513 on xMHC, SNP genotype on IL-8 gene promotor, SNP rs2243250 IL-4 gene,….) are associated with increased recurrence of CDI in this patient population.
time frame: 12 weeks
description: Genetic analysis is performed to describe gene type
arm group label: Intervention group
arm group type: Experimental
description: Recruited patient according inclusion/exclusion criteria
arm group label: Historical control
arm group type: No Intervention
description: Cohort of historical patients matched to study population to serve as control
intervention type: Drug
intervention name: Bezlotoxumab Injection
description: A single dose of Bezlotoxumab (Zinplava) 10mg/kg (actual body weight) 60-minute intravenous infusion during active CDI treatments.
arm group label: Intervention group
other name: No intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Infections
mesh term: Clostridium Infections
mesh term: Recurrence
sharing ipd: No
ipd description: Individual participant data will not be shared