Rifaximin for Monoclonal Gammopathy

Overseen By Madhav Dhodapkar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Antibiotics, Investigational agents

Disqualifiers: Clinical myeloma, Allergic to rifaximin, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well rifaximin, an oral antibiotic, works in treating patients with monoclonal gammopathy. It aims to reduce abnormal blood proteins or cells by killing intestinal bacteria. Rifaximin has been used successfully for CDI treatment but lacks United States Food and Drug Administration approval for this indication.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken antibiotics in the last 3 weeks or be on other investigational agents for gammopathy.

Is Rifaximin generally safe for human use?

There is no specific safety data on Rifaximin in the provided research articles, but it is important to consult with healthcare professionals for safety information specific to your condition. ^{1 2 3 4 5}

How is the drug Rifaximin different from other treatments for monoclonal gammopathy?

Rifaximin is unique because it is an antibiotic primarily used to treat gut-related conditions, and its use for monoclonal gammopathy is novel, as there are no standard treatments specifically for this condition. This makes it different from other treatments like Rituximab, which is a monoclonal antibody used for B-cell related conditions. ^{6 7 8 9 10}

Research Team

Ajay Nooka, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for individuals with monoclonal gammopathy, a condition where abnormal proteins are produced by the immune system. Participants must understand and sign consent, not have received antibiotics in the last 3 weeks or be on other investigational treatments for gammopathy. Women of childbearing potential and men must use contraception during and after the trial.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I have been diagnosed with a blood condition called MGUS.

Patients will be grouped based on the type of protein in their blood: IgA, IgG, or IgM.

Exclusion Criteria

Women of child-bearing potential and men must agree to use adequate contraception 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

I have taken antibiotics in the last 3 weeks.

I am not on any experimental treatments for gammopathy and do not need therapy for clinical myeloma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rifaximin orally thrice daily for 2 weeks

2 weeks

Daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Rifaximin

Trial Overview The study is testing rifaximin, an antibiotic thought to reduce bacteria in the intestines that may be linked to monoclonal gammopathy. The goal is to see if it can decrease abnormal proteins or cells associated with this condition.

Participant Groups

Group I: Treatment (rifaximin) Experimental Treatment 1 Intervention

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

Rifaximin is already approved in United States, Canada, European Union, India for the following indications:

Approved in United States as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in Canada as Zaxine for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in European Union as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in India as Ciboz and Xifapill for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

Findings from Research

Fluoroquinolone antibiotics generally have a favorable safety profile with mostly mild and reversible side effects, but postmarketing studies have revealed severe adverse events linked to some newer agents, leading to market withdrawals or restrictions due to serious risks like liver toxicity.

While older fluoroquinolones like ciprofloxacin and levofloxacin have not shown significant severe adverse events, caution is warranted with newer agents like moxifloxacin and gatifloxacin, as their long-term safety data is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of the fluoroquinolones. Bertino, J., Fish, D.[2006]

A patient developed drug-induced immune hemolytic anemia (DIIHA) after starting metaxalone, presenting with yellow skin and orange urine, highlighting that any medication can potentially cause this condition.

The patient's symptoms significantly improved after stopping metaxalone and starting treatment with glucocorticoids and rituximab, demonstrating effective management of DIIHA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metaxalone-induced Immune Hemolytic Anemia. Onyechi, A., Ohemeng-Dapaah, J., Patel, R., et al.[2023]

A patient with rifampicin-induced thrombocytopenia produced an antibody that specifically binds to the GPIb-IX complex, particularly the GPIX subunit, which was confirmed through various assays including flow cytometry and immunoprecipitation.

The study revealed that the binding site of the rifampicin-dependent antibody overlaps with that of quinine-dependent antibodies, suggesting a shared mechanism of drug-induced thrombocytopenia that could enhance our understanding of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. Burgess, JK., Lopez, JA., Gaudry, LE., et al.[2021]

Rifampin can cause serious side effects, including transient hemolytic anemia and acute renal failure, as demonstrated in a detailed case study.

The case revealed persistent anti-platelet antibodies even three weeks after stopping rifampin, suggesting that immune mechanisms may play a significant role in these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reaction to rifampin: a case with long lasting antiplatelet antibodies. Tricerri, A., Vangeli, M., Addario, C., et al.[2013]

Ciprofloxacin can cause serious side effects, including interstitial nephritis and autoimmune hemolytic anemia, with the combination of both being extremely rare.

In this case, the hemolytic anemia improved after discontinuing ciprofloxacin and starting steroid treatment, but the interstitial nephritis led to irreversible kidney damage and end-stage renal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia. Lim, S., Alam, MG.[2019]

A retrospective review identified 19 patients with persistent hypogammaglobulinaemia after rituximab treatment, showing significantly low IgG levels and an inability to mount immune responses to vaccinations, indicating a potential long-term effect of the drug on immune function.

In an audit of 114 patients treated with rituximab, 23.7% exhibited hypogammaglobulinaemia, highlighting the need for clinicians to monitor for this condition and consider intravenous immunoglobulin (IVIG) therapy, even years after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. Makatsori, M., Kiani-Alikhan, S., Manson, AL., et al.[2015]

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab is a monoclonal antibody designed to target the CD20 antigen on B-lymphocytes, which is crucial for its role in treating lymphoproliferative disorders.

The review identifies four main mechanisms through which rituximab reduces B-lymphocyte populations, although the exact contributions of each mechanism to its overall clinical effectiveness are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[THE MECHANISMS OF ACTION OF RITUXIMAB]. Gil'deeva, GN., Kudlai, DA., Luk'yanov, SV.[2016]

In a study of 177 patients with multisystem autoimmune disease treated with rituximab, 34% developed hypogammaglobulinaemia (low immunoglobulin levels) for at least three consecutive months, but severe infections were not directly linked to these low levels.

The incidence of hypogammaglobulinaemia was more closely associated with prior treatments like cyclophosphamide and glucocorticoids rather than the total dose of rituximab, suggesting that while rituximab is generally safe, careful monitoring is necessary, especially in patients with a history of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease. Marco, H., Smith, RM., Jones, RB., et al.[2022]

In a phase II study involving newly diagnosed multiple myeloma patients, the addition of rituximab to melphalan and prednisone therapy did not improve response rates or event-free survival, indicating limited efficacy of this combination treatment.

Despite no complete remissions, 58% of patients achieved a partial response, and the treatment was generally well-tolerated, with manageable toxicity similar to standard MP chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of rituximab and oral melphalan and prednisone in newly diagnosed multiple myeloma. Baz, R., Fanning, S., Kunkel, L., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The safety profile of the fluoroquinolones. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

Metaxalone-induced Immune Hemolytic Anemia. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

Adverse drug reaction to rifampin: a case with long lasting antiplatelet antibodies. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[THE MECHANISMS OF ACTION OF RITUXIMAB]. [2016]

9. England pubmed.ncbi.nlm.nih.gov

The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Combination of rituximab and oral melphalan and prednisone in newly diagnosed multiple myeloma. [2019]