Blood and Lymph Conditions

Immune System Diseases

All Conditions

Neoplasms

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Monoclonal Gammopathy of Undetermined Significance

Waldenstrom Macroglobulinemia

Paraproteinemias

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hypergammaglobulinemia

Light Chain Deposition Disease

Anti-Infective Agents

Gastrointestinal Agents

All Drugs and Chemicals

Rifaximin

Anti-Bacterial Agents

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

Madhav Dhodapkar, MD

Bryan Burton

Eduardo Sanabria

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.

Rifaximin in Patients With Monoclonal Gammopathy

Pilot Study of Oral Rifaximin in Patients With Monoclonal Gammopathy

Clinical response rate will be calculated as proportion (responders/total patients).

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.

16S sequencing will be used to compare changes in stool microbiota.

Changes in clonal Ig will be used to assess changes in gammopathy.

Emory University

Principal Investigator

Nutritional and Metabolic Diseases

Multiple Myeloma

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

AL Amyloidosis

Raymond Comenzo, MD

This protocol seeks to enroll smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significant (MGUS) patients with λ light chain (LC) involvement, a group of patients for whom standard of care is observation not treatment. Patients with SMM and MGUS have a precursor plasma cell disorder from which light chain amyloidosis (AL) can evolve. In this trial, enrolled subjects will have blood and if available bone marrow cells evaluated by molecular testing to determine their clonal λ LC variable region (VL) germline gene. Seventy percent of AL cases involve just 7 germline donors, 5 of which are λ germline donors. The hypothesis that will be tested with this protocol is that the presence of AL germline genes associated with AL in patients with a pre-existing diagnosis of λ SMM or λ MGUS indicates the presence of AL or risk of progression to AL.

In this trial up to 200 patients with either λ light chain (LC) monoclonal gammopathy of undetermined significance (MGUS) or λ LC smoldering multiple myeloma (SMM) with a κ::λ LC ratio \< 0.26 and whose λ minus κ LC difference (dFLC) is greater than 23 mg/L will be recruited. Heavy chain type will not affect patient eligibility as long as the involved LC is λ type.

Patients may learn about the trial through internet advertisements and contact the data manager to receive the study's enrollment documents. Patient recruitment will be open to all eligible patient within the United States. Informed consent may be obtained in person or by phone. After the patient has completed a HIPPA release form, the patient's physician will be contacted and informed of the patient's consent to this study and will be asked to provide medical records for screening. If the patient is found eligible, the patient and physician will be informed of the required samples for the protocol, which include peripheral blood and marrow aspirate, if available, with both taken during routine clinical procedures. Prepaid FedEx boxes will be provided by the study to ship research samples to Tufts Medical Center for remote patients.

Both the peripheral blood and marrow samples will be tested for the presence of variable region (VL) germline genes in our Tufts Medical Center laboratory. In addition, plasma isolated from the peripheral blood sample (as well as the corresponding identified germline gene) will be sent to the laboratory of Dr. Jonathan Wall at the University of Tennessee for assay analysis. The assay will seek to distinguish the presence of amyloidogenic vs. non-amyloidogenic light chains. Germline gene results from Tufts Medical Center will be shared with patients and their physicians; however, University of Tennessee assay analysis will not be shared due to its experimental nature.

The analysis of this trial will be based on the frequency with which enrolled MGUS and SMM patients are found to have genes associated with light chain amyloidosis (AL), are found to have asymptomatic AL or symptomatic AL, or progress to AL. The diagnosis of AL is a tissue diagnosis. If amyloidosis is suspected at any time during a subject's participation, their physician will be contacted and given recommendations regarding diagnostic tests and disease staging.

Bone marrow and peripheral blood samples.

A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early

After sequencing of their light chain (LC) variable region (VL) germline gene, subjects with light chain amyloidosis (AL) associated sequences will be followed for up to 5 years to monitor the potential progression of their disease to AL amyloidosis.

Tufts Medical Center

Smoldering Multiple Myeloma

Precancerous Conditions

Antineoplastic Agents

Antibodies

Daratumumab

Immunoglobulins

Daratumumab will be administered by IV infusion weekly during cycles 1 and 2 Daratumumab will be administered by IV infusion every other week during cycles 3 through 6 Daratumumab will be administered by IV infusion monthly during cycles 7 through 20

Daratumumab is a drug that may kill or stop cancer cells from growing through a variety of mechanisms by attaching to the CD38 molecule

Irene Ghobrial, MD

This research study is studying a drug as a possible treatment for Monoclonal Gammopathy of Unknown Significance (MGUS) or Smoldering Multiple Myeloma (SMM).

The drug involved in this study is:

-Daratumumab

This research study is a Phase II clinical trial, which tests the effectiveness of an investigational drug. Preliminary experience suggests that daratumumab may prevent or postpone SMM from becoming active multiple myeloma. The purpose of this research study is to determine if the this drug may improve the rate of prevention of multiple myeloma.

Multiple myeloma is a cancer of the plasma cell, which is an important part of the immune system. Patients with active multiple myeloma generally require treatment. There are currently no approved therapies for smoldering multiple myeloma or Monoclonal Gammopathy of Unknown Significance.

Daratumumab is a drug that may kill or stop cancer cells from growing through a variety of mechanisms by attaching to the CD38 molecule, which is over-expressed in multiple myeloma cells. This type of drug is called a monoclonal antibody. The FDA (the U.S. Food and Drug Administration) has not approved Daratumumab for the participant specific disease but it has been approved for use in active Multiple Myeloma.

Phase II Study of the CD38 Antibody Daratumumab in Patients With High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

A Phase II Study of the CD38 Antibody Daratumumab in Patients With High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

To determine the proportion of patients who are in VGPR or better after twenty cycles of therapy with Daratumumab. This will be determined at the time of best overall response. The estimate and the two-sided 90% binomial confidence interval will be provided in the analysis.

The objective response rate (partial response or better according to the modified IMWG criteria) and the proportion of patients with a MRD, CR, PR or MR will be reported with 90% exact binominal confidence interval (CI). The exact two-sided 90% CI around response rate will be no wider than 28% with 40 eligible patients.

To estimate the duration of response (time from objective response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died) the Kaplan-Meier method will be used.

The duration of overall CR is progression or death. Patients who have not progressed or died are censored at the date last known progression-free.

The duration of overall response is measured as the time from initiation of first response to first documentation of disease progression or death. Patients who have not progressed or died are censored at the date last known progression-free.

PFS is defined as the time from first-dose to the disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free.

Safety analysis will be conducted using the Safety Population defined as any patient receiving one dose of study treatment. For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rifaximin in Patients With Monoclonal Gammopathy	NCT03820817	IgA Monoclonal ... IgG Monoclonal ... IgM Monoclonal ... Light Chain Dep... Monoclonal Gamm... Smoldering Wald... Waldenstrom Mac... Gammopathy, Mon... Gammopathy Igg	Rifaximin	18 Years -	Emory University
Rifaximin in Patients With Monoclonal Gammopathy	NCT03820817	IgA Monoclonal ... IgG Monoclonal ... IgM Monoclonal ... Light Chain Dep... Monoclonal Gamm... Smoldering Wald... Waldenstrom Mac... Gammopathy, Mon... Gammopathy Igg	Rifaximin	18 Years -	Emory University
A Diagnostic Screening Trial Seeking AL Amyloidosis Very Early	NCT02741999	Plasma Cell Dys... Monoclonal Gamm...		18 Years - 99 Years	Tufts Medical Center
Phase II Study of the CD38 Antibody Daratumumab in Patients With High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma	NCT03236428	Monoclonal Gamm... Smoldering Mult...	Daratumumab	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for monoclonal gammopathy