<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/NCT03768869</url>
  </required_header>
  <id_info>
    <org_study_id>05-0300.cc</org_study_id>
    <nct_id>NCT03768869</nct_id>
  </id_info>
  <brief_title>Fever and Neutropenia in Pediatric Oncology Patients</brief_title>
  <official_title>Fever and Neutropenia in Pediatric Oncology Patients: A Randomized, Controlled, Multi-Center Study of Outpatient Therapy Evaluation of Genomic and Proteomic Correlates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is possible to distinguish between pediatric oncology patients who are at high or low risk&#xD;
      for serious infection during periods of fever and treatment related neutropenia based on&#xD;
      clinical parameters. Patients with low risk can be safely treated as outpatients primarily&#xD;
      using oral antibiotics. It is possible to improve methods of risk stratification through the&#xD;
      addition of genomic and proteomic factors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Outpatient management of patients considered to be at low risk for serious bacterial&#xD;
      infection has been explored using risk stratification schema based on clinical parameters.&#xD;
      First, patients will be stratified based on a clinical risk stratification schema. Patients&#xD;
      stratified to the low risk group will be randomized between treatment using standard&#xD;
      inpatient intravenous antibiotic therapy or outpatient antibiotic therapy using primarily an&#xD;
      oral regimen. Second, an evaluation of proteins important to the innate immune system will be&#xD;
      performed to provide a molecular characterization of episodes based on etiology. Third,&#xD;
      single nucleotide polymorphisms in genes important for innate immunity will be evaluated to&#xD;
      determine effect of each on infection risk during treatment induced neutropenia. Finally, we&#xD;
      will develop a bank of both plasma and DNA specimens correlated with clinical outcomes for&#xD;
      future use.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Insufficient data to answer the study question&#xD;
  </why_stopped>
  <start_date type="Actual">February 2006</start_date>
  <completion_date type="Actual">April 3, 2009</completion_date>
  <primary_completion_date type="Actual">April 3, 2009</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be stratified as high risk, where they will receive inpatient management, or low risk, where they will then be randomize to receive inpatient or outpatient management.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Because inpatient management and outpatient management use different treatment methods, blinding is not possible.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Low Risk Treatment</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>The response to initial antibiotic management without modification with regards to resolution of the episode of fever and neutropenia, measured through blood cultures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Protein Evaluation</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>Comparison of the level of each protein at the initiation of each episode versus resolution to determine if there is a pattern of proteins that correlates with an infectious outcome, measured using ELISA techniques</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Genomics Evaluation</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>A comparison of proven infections between patients with the wild-type and variant forms of each gene studied, taken through DNA specimens</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cost Benefit Analysis</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>A cost-benefit analysis between the arms, duration of fever per episode between the arms, and number of admissions or deaths. Medical cost will be obtained through billing records and indirect costs will be estimated through information obtained from the family.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein Evaluation</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>Determine trends of protein markers on days 3 and 5 of evaluation, using ELISA techniques.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genomics Evaluation</measure>
    <time_frame>Start of study to end of study, up to two years</time_frame>
    <description>A comparison of the number of episodes of fever and neutropenia per patient and the duration of fever per episode between the wild type and variant forms of each gene, taken through DNA specimens.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Fever</condition>
  <condition>Neutropenia</condition>
  <arm_group>
    <arm_group_label>Low Risk: Oupatient Management</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Risk: Inpatient Management</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Risk: Inpatient Management</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low Risk: Oupatient Management</intervention_name>
    <description>Intravenous Levaquin initially, then oral dosing. Patient discharged to go home to finish medication cycle after initial 120 minutes observation. Patients will be evaluated daily in the clinic, and his or her temperature must be taken and recorded four times per day. Blood cultures will be drawn at clinic visits.</description>
    <arm_group_label>Low Risk: Oupatient Management</arm_group_label>
    <other_name>Oral Antibiotics</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low Risk: Inpatient Management</intervention_name>
    <description>Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.</description>
    <arm_group_label>Low Risk: Inpatient Management</arm_group_label>
    <other_name>IV Antibiotics</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High Risk: Inpatient Management</intervention_name>
    <description>Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.</description>
    <arm_group_label>High Risk: Inpatient Management</arm_group_label>
    <other_name>IV Antibiotics, High Risk</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Any pediatric patient age &lt;21 years with an oncology diagnosis who is undergoing therapy&#xD;
        and is expected to have treatment related neutropenia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any patient who has previously undergone autologous or allogeneic bone marrow&#xD;
             transplant will be excluded from study enrollment. If a patient is expected to undergo&#xD;
             autologous or allogeneic bone marrow transplant as part of therapy at some point after&#xD;
             enrollment in the study he/she will be removed from the study at the start of their&#xD;
             bone marrow transplant.&#xD;
&#xD;
          2. Any patient with a documented allergy to Levofloxacin or any other fluoroquinolone&#xD;
             will be excluded.&#xD;
&#xD;
          3. Patients with a known pregnancy will be excluded.&#xD;
&#xD;
          4. Any patient with an underlying chronic musculoskeletal condition (ie Juvenile&#xD;
             rheumatoid arthritis, Systemic lupus erythematosis etc) which may make evaluation for&#xD;
             joint toxicity related to quinolone treatment difficult.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kelly Maloney, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Colorado</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>April 23, 2021</last_update_submitted>
  <last_update_submitted_qc>April 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pediatrics</keyword>
  <keyword>Oncology</keyword>
  <keyword>Outpatient therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neutropenia</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Antibiotics, Antitubercular</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/NCT03768869
org study id: 05-0300.cc
nct id: NCT03768869
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
It is possible to distinguish between pediatric oncology patients who are at high or low risk
      for serious infection during periods of fever and treatment related neutropenia based on
      clinical parameters. Patients with low risk can be safely treated as outpatients primarily
      using oral antibiotics. It is possible to improve methods of risk stratification through the
      addition of genomic and proteomic factors.
Outpatient management of patients considered to be at low risk for serious bacterial
      infection has been explored using risk stratification schema based on clinical parameters.
      First, patients will be stratified based on a clinical risk stratification schema. Patients
      stratified to the low risk group will be randomized between treatment using standard
      inpatient intravenous antibiotic therapy or outpatient antibiotic therapy using primarily an
      oral regimen. Second, an evaluation of proteins important to the innate immune system will be
      performed to provide a molecular characterization of episodes based on etiology. Third,
      single nucleotide polymorphisms in genes important for innate immunity will be evaluated to
      determine effect of each on infection risk during treatment induced neutropenia. Finally, we
      will develop a bank of both plasma and DNA specimens correlated with clinical outcomes for
      future use.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be stratified as high risk, where they will receive inpatient management, or low risk, where they will then be randomize to receive inpatient or outpatient management.
primary purpose: Supportive Care
masking: None (Open Label)
masking description: Because inpatient management and outpatient management use different treatment methods, blinding is not possible.
measure: Low Risk Treatment
time frame: Start of study to end of study, up to two years
description: The response to initial antibiotic management without modification with regards to resolution of the episode of fever and neutropenia, measured through blood cultures
measure: Protein Evaluation
time frame: Start of study to end of study, up to two years
description: Comparison of the level of each protein at the initiation of each episode versus resolution to determine if there is a pattern of proteins that correlates with an infectious outcome, measured using ELISA techniques
measure: Genomics Evaluation
time frame: Start of study to end of study, up to two years
description: A comparison of proven infections between patients with the wild-type and variant forms of each gene studied, taken through DNA specimens
measure: Cost Benefit Analysis
time frame: Start of study to end of study, up to two years
description: A cost-benefit analysis between the arms, duration of fever per episode between the arms, and number of admissions or deaths. Medical cost will be obtained through billing records and indirect costs will be estimated through information obtained from the family.
measure: Protein Evaluation
time frame: Start of study to end of study, up to two years
description: Determine trends of protein markers on days 3 and 5 of evaluation, using ELISA techniques.
measure: Genomics Evaluation
time frame: Start of study to end of study, up to two years
description: A comparison of the number of episodes of fever and neutropenia per patient and the duration of fever per episode between the wild type and variant forms of each gene, taken through DNA specimens.
arm group label: Low Risk: Oupatient Management
arm group type: Experimental
description: Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.
arm group label: Low Risk: Inpatient Management
arm group type: Active Comparator
description: Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.
arm group label: High Risk: Inpatient Management
arm group type: Active Comparator
description: Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.
intervention type: Drug
intervention name: Low Risk: Oupatient Management
description: Intravenous Levaquin initially, then oral dosing. Patient discharged to go home to finish medication cycle after initial 120 minutes observation. Patients will be evaluated daily in the clinic, and his or her temperature must be taken and recorded four times per day. Blood cultures will be drawn at clinic visits.
arm group label: Low Risk: Oupatient Management
other name: Oral Antibiotics
intervention type: Drug
intervention name: Low Risk: Inpatient Management
description: Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.
arm group label: Low Risk: Inpatient Management
other name: IV Antibiotics
intervention type: Drug
intervention name: High Risk: Inpatient Management
description: Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.
arm group label: High Risk: Inpatient Management
other name: IV Antibiotics, High Risk
criteria: 
gender: All
minimum age: 0 Years
maximum age: 21 Years
healthy volunteers: No
last name: Kelly Maloney, MD
role: Principal Investigator
affiliation: Children's Hospital Colorado
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neutropenia
mesh term: Fever
mesh term: Anti-Bacterial Agents
mesh term: Antibiotics, Antitubercular