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.

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