This phase II trial compares the effect of rifaximin to no intervention for the treatment of IgA monoclonal gammopathy of undetermined significance (MGUS). Rifaximin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's DNA and may kill cancer cells or precancerous cells like those found with MGUS. Giving rifaximin may kill more precancerous cells in patients with IgA MGUS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive rifaximin orally (PO) three times daily (TID) for 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

ARM B: Patients undergo blood sample collection throughout the study.

After completion of study intervention, patients are followed up at 90 days.

Inclusion Criteria:

• Age ≥ 18 years

• Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants

• Clinical diagnosis of IgA monoclonal gammopathy of undetermined significance (MGUS) based on International Myeloma Working Group (IMWG)-2014 criteria (Rajkumar et al, Lancet Oncology, 2014)

• Agree to use adequate contraception

  • For women of child-bearing potential: prior to study entry and for the duration of study participation
  • For men: prior to study entry, for the duration of study participation, and one month after completion of rifaximin administration (for men)

• No antibiotic use in the preceding 2 weeks

Exclusion Criteria:

• Participants who are receiving other investigational agents
• Pregnant women
• Known hypersensitivity to rifaximin