Rifaximin in Patients With Monoclonal Gammopathy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pilot Study of Oral Rifaximin in Patients With Monoclonal Gammopathy

Conditions
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IgA Monoclonal Gammopathy, IgG Monoclonal Gammopathy, IgM Monoclonal Gammopathy, Light Chain Deposition Disease, Monoclonal Gammopathy, Smoldering Waldenstrom Macroglobulinemia, Waldenstrom Macroglobulinemia, Gammopathy, Monoclonal, Gammopathy Igg

Intervention / Treatment
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* Drug: Rifaximin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |