Metformin XR for Monoclonal Gammopathy of Undetermined Significance

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Dana-Farber at Merrimack Valley, Methuen, MA
Monoclonal Gammopathy of Undetermined Significance+4 More
Metformin XR - Drug
Eligibility
18+
All Sexes
Eligible conditions
Select

Study Summary

Investigation of Metformin for the Prevention of Progression of Precursor Multiple Myeloma

See full description

Eligible Conditions

  • Monoclonal Gammopathy of Undetermined Significance
  • Smoldering Multiple Myeloma

Treatment Effectiveness

Effectiveness Progress

1 of 3

Other trials for Monoclonal Gammopathy of Undetermined Significance

Study Objectives

This trial is evaluating whether Metformin XR will improve 1 primary outcome and 9 secondary outcomes in patients with Monoclonal Gammopathy of Undetermined Significance. Measurement will happen over the course of Baseline to 6-months.

Baseline to 6-months
(M-)protein concentrations/light chains change
(M-)protein concentrations/light chains change by mass spectrometry
Changes in PROMIS Global Health Summary Score v1.2
Changes in plasma metabolites measured by liquid chromatography-mass spectrometry
Hemoglobin A1c (HbA1c) concentrations change
Hemoglobin concentrations change
Molecular evolution of CD138+ cells
Molecular evolution of immune cells (CD138- or CD45+)
Baseline- 12 months
Changes in response for those who choose to take metformin for up to 1 year per IMWG response criteria
Number of participants willing to continue to take metformin beyond 6 month primary assessment period

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Other trials for Monoclonal Gammopathy of Undetermined Significance

Trial Design

2 Treatment Groups

Placebo
1 of 2
Metformin
1 of 2
Experimental Treatment

This trial requires 80 total participants across 2 different treatment groups

This trial involves 2 different treatments. Metformin XR is the primary treatment being studied. Participants will be divided into 2 treatment groups. Some patients will receive a placebo treatment. The treatments being tested are in Phase 2 and have already been tested with other people.

Placebo
Other
Randomly assigned participants receive a stepped dose escalation until target daily dose of 3 pills/day is reached. The intervention duration will last 6 months.
Metformin
Drug
Randomly assigned participants receive a stepped dose escalation until target daily dose of 1500mg Metformin XR is reached (3 x 500mg pills/day). The intervention duration will last an additional 6 months. Metformin Extension: Participants will have the option of unblinding at the end of their 6months treatment and those who were randomly assigned to the metformin experimental arm can continue taking metformin if they opt in. The extended intervention duration will last an additional 6 months. (1500mg Metformin XR or highest tolerated dose )
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Metformin
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline- 12 months
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly baseline- 12 months for reporting.

Who is running the study

Principal Investigator
O. N.
Omar Nadeem, Principal Investigator
Dana-Farber Cancer Institute

Closest Location

Dana-Farber at Merrimack Valley - Methuen, MA

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 3 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
--Higher-Risk MGUS: bone marrow plasma cell concentration <10%# AND either serum M-protein level ≥1.5 g/dL to <3 g/dL or abnormal free light-chain (FLC) ratio (<0.26 or>1.65) or IgA MGUS.
Note: individuals with an abnormal FLC ratio that are classified as light-chain only are eligible. Light-chain only patients are defined as complete loss of immunoglobulin heavy-chain, accompanied by abnormal FLC ratio with an increased level of the appropriate involved light-chain (increased kappa FLC in patient with ratio >1.65, and increased lambda FLC in patients with ratio <0.26).
The diagnosis of smoldering myeloma is based on the presence of ≥10% plasma cells in the bone marrow. show original

Patient Q&A Section

What are the signs of monoclonal gammopathy of undetermined significance?

"Patients with MGUS have no specific clinical signs or symptoms (though it is uncommon to remain asymptomatic for an extended period of time due to multiple small subclinical organ failures of the adaptive immune system); thus, the presence of monoclonal IgM in blood should be regarded as a clue to the underlying disease. MGUS patients exhibit a high rate of evolving to MGUS and, if left untreated, then to myeloma. The MGUS diagnosis should be made at the time of blood testing, even if the result does not indicate the presence of monoclonal IgM; the latter is only indicated within 6 months of initiating a therapy that inhibits the production of the IgM paraprotein (e.g." - Anonymous Online Contributor

Unverified Answer

How many people get monoclonal gammopathy of undetermined significance a year in the United States?

"The incidence of MMUS is increasing. Men are more often affected by MMUS, probably reflecting a higher prevalence of prostate cancer in men than in women. The presence of MMUS does not indicate increased cardiovascular risk and does not preclude curative treatment." - Anonymous Online Contributor

Unverified Answer

Can monoclonal gammopathy of undetermined significance be cured?

"Results from a recent clinical trial in our small cohort (N = 4) suggest that MOGUS cannot be eradicated, because of its persistence despite treatment. However, they are encouraging since MOGUS may be a benign monoclonal clonal phenomenon, and long-lasting remission even after initiation of active therapy has to be verified in a larger cohort." - Anonymous Online Contributor

Unverified Answer

What causes monoclonal gammopathy of undetermined significance?

"Monoclonal gammopathy of undetermined significance (MGUS) is characterized by a variable accumulation of a monoclonal immunoglobulin in blood. We hypothesize that the increased activity of monocyte/macrophage-derived interleukin 6 (IL-6) is a key step in its development." - Anonymous Online Contributor

Unverified Answer

What is monoclonal gammopathy of undetermined significance?

"MGUS is a monoclonal plasma cell disorder characterized by a proliferative plasma cell response to a previously unexposed antigen. It accounts for 85-90% of plasma cell dyscrasias after polyclonal response to an antigen. MGUS is most often detected as a incidental finding because its signs, symptoms, and complications are similar to those of a normal condition." - Anonymous Online Contributor

Unverified Answer

What are common treatments for monoclonal gammopathy of undetermined significance?

"Patients with M-UMG and/or M/M may benefit from immunosuppressive medication (including calcineurin inhibitors and steroidal immunosuppressants), but patients with more frequent and intense B cell stimulation may benefit from immunostimulatory therapy (e.g., rituximab)." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating monoclonal gammopathy of undetermined significance?

"The first monoclonal gammopathy of undetermined significance-related blood test resulted in an antibody test to evaluate for the presence of a monoclonal gammopathy, however, it did not help diagnose a specific disorder. For the diagnosis of multiple myeloma, it was necessary for a patient to demonstrate clonal gammopathy, low concentration of monoclonal IgM protein in their urine/serum, and bone marrow plasma cell dysplasia in order to be diagnosed with multiple myeloma. The only screening test has been found to have high sensitivity and specificity, which means it will not miss or make a diagnosis when a person doesn't have cancer." - Anonymous Online Contributor

Unverified Answer

How does metformin xr work?

"Metformin-XR does not help, but significantly increase plasma glucose levels as compared with metformin; therefore, it should be avoided in patients who have any diabetic disturbances." - Anonymous Online Contributor

Unverified Answer

Who should consider clinical trials for monoclonal gammopathy of undetermined significance?

"The majority of respondents believed that clinical trials for MGUS should include patients who should be candidates for curative therapy, although opinions varied on the optimal frequency at which such therapy should be offered." - Anonymous Online Contributor

Unverified Answer

Does monoclonal gammopathy of undetermined significance run in families?

"The presence of MGUS/MZH did not significantly impact family cancer risk. However, these results might not be as strong as they looked when this was evaluated in a cohort study." - Anonymous Online Contributor

Unverified Answer

What does metformin xr usually treat?

"Patients treated with metformin xr were younger and healthier than those receiving placebo. Only one serious adverse event was reported (hemorrhage) in association with both treatments. There were no patients reported with lactic acidosis and no reported cardiovascular conditions. Because of its safety and the need for a new treatment for MUG, we recommend metformin xr for the treatment of MUG, the first new agent for this disease reported in more than 20 years." - Anonymous Online Contributor

Unverified Answer

What is the survival rate for monoclonal gammopathy of undetermined significance?

"Patients with MGUS have an early average survival rate of approximately 4.0 years, and those with overt MM have an additional risk factor of mortality. If MGUS is diagnosed at or before the onset of MM, the average survival rate is much higher. Thus, MGUS should be considered a precancerous condition, and not a mere diagnosis of 'Monoclonal gammopathy of undetermined significance." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
See if you qualify for this trial
Get access to this novel treatment for Monoclonal Gammopathy of Undetermined Significance by sharing your contact details with the study coordinator.