<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/NCT03820817</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00106380</org_study_id>
    <secondary_id>NCI-2018-02106</secondary_id>
    <secondary_id>Winship4480-18</secondary_id>
    <nct_id>NCT03820817</nct_id>
  </id_info>
  <brief_title>Rifaximin in Patients With Monoclonal Gammopathy</brief_title>
  <official_title>Pilot Study of Oral Rifaximin in Patients With Monoclonal Gammopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Emory University</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 trial studies how well rifaximin works in treating patients with monoclonal gammopathy.&#xD;
      Antibiotics, such as rifaximin, may help to kill bacteria in the intestines and reduce the&#xD;
      abnormal protein or cells in patients with monoclonal gammopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the effect of a 2-week course of rifaximin on clonal immunoglobulin (Ig) in&#xD;
      patients with monoclonal gammopathy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate safety and tolerability of a 2-week course of rifaximin.&#xD;
&#xD;
      II. To evaluate changes in stool microbiota by 16S ribosomal ribonucleic acid (rRNA) gene&#xD;
      (16S) sequencing.&#xD;
&#xD;
      III. To evaluate changes in gammopathy as assessed by changes in clonal Ig and/or plasma&#xD;
      cells.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive rifaximin orally (PO) thrice daily (TID) on days 1-14 in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed for 8 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 15, 2019</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response rate defined as a reduction in clonal immunoglobulin (Ig) by &gt; 25%</measure>
    <time_frame>Up to 2 weeks after study start</time_frame>
    <description>Clinical response rate will be calculated as proportion (responders/total patients).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>Up to 12 weeks after study start</time_frame>
    <description>Incidence of adverse events (AEs) occurring during the study will be summarized by system organ class and preferred term. Adverse events will also be summarized by causality and grade. Serious adverse events will be listed separately.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in stool microbiota</measure>
    <time_frame>Up to 12 weeks after study start</time_frame>
    <description>16S sequencing will be used to compare changes in stool microbiota.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gammopathy</measure>
    <time_frame>Up to 12 weeks after study start</time_frame>
    <description>Changes in clonal Ig will be used to assess changes in gammopathy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>IgA Monoclonal Gammopathy</condition>
  <condition>IgG Monoclonal Gammopathy</condition>
  <condition>IgM Monoclonal Gammopathy</condition>
  <condition>Light Chain Deposition Disease</condition>
  <condition>Monoclonal Gammopathy</condition>
  <condition>Smoldering Waldenstrom Macroglobulinemia</condition>
  <condition>Waldenstrom Macroglobulinemia</condition>
  <condition>Gammopathy, Monoclonal</condition>
  <condition>Gammopathy Igg</condition>
  <arm_group>
    <arm_group_label>Treatment (rifaximin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive rifaximin PO TID on days 1-14 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifaximin</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (rifaximin)</arm_group_label>
    <other_name>Xifaxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of monoclonal gammopathy of undetermined significance based on&#xD;
             International Myeloma Working Group (IMWG) criteria&#xD;
&#xD;
          -  Patients will be enrolled into one of 3 cohorts:&#xD;
&#xD;
               -  Cohort A: IgA gammopathy&#xD;
&#xD;
               -  Cohort B: IgG gammopathy / or light chain gammopathy&#xD;
&#xD;
               -  Cohort C: IgM gammopathy / asymptomatic macroglobulinemia&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received antibiotics within last 3 weeks&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents for gammopathy. Patients&#xD;
             with clinical myeloma requiring anti-myeloma therapy are also excluded&#xD;
&#xD;
          -  History of allergic reactions or intolerance attributed to rifaximin or compounds of&#xD;
             similar chemical or biologic composition to antibiotic under study&#xD;
&#xD;
          -  The effects of rifaximin on the developing human fetus are unknown. For this reason,&#xD;
             women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and 4 months after completion of rifaximin administration&#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_official>
    <last_name>Madhav Dhodapkar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Madhav Dhodapkar, MD</last_name>
    <phone>404-778-4191</phone>
    <email>madhav.v.dhodapkar@emory.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bryan Burton</last_name>
      <phone>404-778-3612</phone>
      <email>bryan.james.burton@emory.edy</email>
    </contact>
    <contact_backup>
      <last_name>Eduardo Sanabria</last_name>
      <phone>404-778-2164</phone>
      <email>esanab2@emory.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Madhav Dhodapkar</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Paraproteinemias</mesh_term>
    <mesh_term>Monoclonal Gammopathy of Undetermined Significance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rifaximin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03820817
org study id: IRB00106380
secondary id: NCI-2018-02106
secondary id: Winship4480-18
nct id: NCT03820817
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This trial studies how well rifaximin works in treating patients with monoclonal gammopathy.
      Antibiotics, such as rifaximin, may help to kill bacteria in the intestines and reduce the
      abnormal protein or cells in patients with monoclonal gammopathy.
PRIMARY OBJECTIVE:

      I. To evaluate the effect of a 2-week course of rifaximin on clonal immunoglobulin (Ig) in
      patients with monoclonal gammopathy.

      SECONDARY OBJECTIVES:

      I. To evaluate safety and tolerability of a 2-week course of rifaximin.

      II. To evaluate changes in stool microbiota by 16S ribosomal ribonucleic acid (rRNA) gene
      (16S) sequencing.

      III. To evaluate changes in gammopathy as assessed by changes in clonal Ig and/or plasma
      cells.

      OUTLINE:

      Patients receive rifaximin orally (PO) thrice daily (TID) on days 1-14 in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed for 8 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical response rate defined as a reduction in clonal immunoglobulin (Ig) by > 25%
time frame: Up to 2 weeks after study start
description: Clinical response rate will be calculated as proportion (responders/total patients).
measure: Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: Up to 12 weeks after study start
description: Incidence of adverse events (AEs) occurring during the study will be summarized by system organ class and preferred term. Adverse events will also be summarized by causality and grade. Serious adverse events will be listed separately.
measure: Changes in stool microbiota
time frame: Up to 12 weeks after study start
description: 16S sequencing will be used to compare changes in stool microbiota.
measure: Changes in gammopathy
time frame: Up to 12 weeks after study start
description: Changes in clonal Ig will be used to assess changes in gammopathy.
arm group label: Treatment (rifaximin)
arm group type: Experimental
description: Patients receive rifaximin PO TID on days 1-14 in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Rifaximin
description: Given PO
arm group label: Treatment (rifaximin)
other name: Xifaxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Madhav Dhodapkar, MD
role: Principal Investigator
affiliation: Emory University
last name: Madhav Dhodapkar, MD
phone: 404-778-4191
email: madhav.v.dhodapkar@emory.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Madhav Dhodapkar
investigator title: Principal Investigator
mesh term: Waldenstrom Macroglobulinemia
mesh term: Paraproteinemias
mesh term: Monoclonal Gammopathy of Undetermined Significance
mesh term: Rifaximin
sharing ipd: No