Rifaximin in Patients With Monoclonal Gammopathy

Pilot Study of Oral Rifaximin in Patients With Monoclonal Gammopathy

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.

Study Overview

• Status: Recruiting
• Conditions: Waldenstrom Macroglobulinemia; Light Chain Deposition Disease; IgA Monoclonal Gammopathy; IgG Monoclonal Gammopathy; IgM Monoclonal Gammopathy; Monoclonal Gammopathy; Smoldering Waldenstrom Macroglobulinemia; Gammopathy, Monoclonal; Gammopathy Igg
• Intervention / Treatment: Drug: Rifaximin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Madhav Dhodapkar, MD; Phone Number: 404-778-4191; Email: madhav.v.dhodapkar@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Contact: Eduardo Sanabria; Phone Number: 404-778-2164; Email: esanab2@emory.edu
      • Contact: Bryan Burton; Phone Number: 404-778-3612; Email: bryan.james.burton@emory.edy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of monoclonal gammopathy of undetermined significance based on International Myeloma Working Group (IMWG) criteria

• Patients will be enrolled into one of 3 cohorts:

  • Cohort A: IgA gammopathy
  • Cohort B: IgG gammopathy / or light chain gammopathy
  • Cohort C: IgM gammopathy / asymptomatic macroglobulinemia
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have received antibiotics within last 3 weeks
• Patients who are receiving any other investigational agents for gammopathy. Patients with clinical myeloma requiring anti-myeloma therapy are also excluded
• History of allergic reactions or intolerance attributed to rifaximin or compounds of similar chemical or biologic composition to antibiotic under study
• The effects of rifaximin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of rifaximin administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (rifaximin); Patients receive rifaximin PO TID on days 1-14 in the absence of disease progression or unacceptable toxicity.	Drug: Rifaximin; Given PO; Other Names: Xifaxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response rate defined as a reduction in clonal immunoglobulin (Ig) by > 25%	Clinical response rate will be calculated as proportion (responders/total patients).	Up to 2 weeks after study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	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.	Up to 12 weeks after study start
Changes in stool microbiota	16S sequencing will be used to compare changes in stool microbiota.	Up to 12 weeks after study start
Changes in gammopathy	Changes in clonal Ig will be used to assess changes in gammopathy.	Up to 12 weeks after study start

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: The Leukemia and Lymphoma Society
• Investigators: Principal Investigator: Madhav Dhodapkar, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Protein Disorders; Neoplasms, Plasma Cell; Hypergammaglobulinemia; Waldenstrom Macroglobulinemia; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: IRB00106380; NCI-2018-02106 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Winship4480-18 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No