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

NCT04850846 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 21-008K22CA251648
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this research is to understand whether the drug metformin could be used in the future to help prevent patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) from developing multiple myeloma. The names of the study drug involved in this study is:

• Metformin, extended release
• Placebo ( a pill that has no active ingredients)

Conditions

Smoldering Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance

Keywords

Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• (M-)Protein Concentrations Change

  Assessed by using the serum-protein electrophoresis

  Baseline to 6-months

Secondary Outcomes (9)

• Serum Free Light Chains Change by Mass Spectrometry

  Baseline to 6-months

• Hemoglobin Concentrations Change

  Baseline to 6-months

• Hemoglobin A1c (HbA1c) Concentrations Change

  Baseline to 6-months

• Molecular Evolution of CD138+ Cells

  Baseline to 6-months

• Molecular Evolution of Immune Cells (CD138- or CD45+)

  Baseline to 6-months

Study Arms (2)

Metformin

EXPERIMENTAL

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 )

Drug: Metformin XR

Placebo

EXPERIMENTAL

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.

Other: Placebo

Interventions

Metformin XR DRUG

Orally by mouth

Also known as: Glucophage XR

Metformin

Placebo OTHER

Orally by mouth

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with higher-risk MGUS or low-risk SMM defined below:
• 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).

You may not qualify if:

• #A new bone marrow biopsy is preferred for plasma cell determination at screening; however, determination of eligibility can be made from most recent bone marrow biopsy performed as long as it was within 2 years of enrollment.
• Absence of evidence of CRAB criteria\* or new criteria of active MM or active WM which including the following (note if one or more criteria has not been evaluated (e.g., no MRI), the criteria for active MM or WM for that feature is considered unmet):
• Increased calcium levels (corrected serum calcium \>0.25 mmol/dL above the upper limit of normal or \>.275 mmol/dL) related to MM
• Renal insufficiency (attributable to MM)
• Anemia (Hb 2g/dL below the lower limit of normal or \<10g/dL) related to MM
• Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)
• Bone marrow plasma cells ≥60%
• MRI with two or more focal lesion that is at least 5 mm or greater in size
• \*Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• The following laboratory values obtained prior to the first dose of study drug/placebo:
• AST and ALT \< 1.5 x institutional ULN
• Serum bilirubin \< institutional ULN (in patients with Gilbert's Disease, direct bilirubin \< institutional ULN)
• Calculated creatinine clearance ≥ 45 mL/min

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber at Brighton

Brighton, Massachusetts, 02135, United States

Location

Dana-Farber at Merrimack Valley

Methuen, Massachusetts, 01844, United States

Location

Dana-Farber at Milford

Milford, Massachusetts, 01757, United States

Location

DF/ BWCC in Clinical Affiliation with South Shore Hospital

Weymouth, Massachusetts, 02190, United States

Location

Dana-Farber at NHOH

Londonderry, New Hampshire, 35053, United States

Location

MeSH Terms

Conditions

Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Dana-Farber Cancer Institute

CatherineR_Marinac@DFCI.HARVARD.EDU

6176324703

Study Officials

• Omar Nadeem, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

• Catherine R Marinac, PhD

  Dana-Farber Cancer Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: April 20, 2021
• Study Start: April 27, 2021
• Primary Completion: January 29, 2025
• Study Completion (Estimated): July 31, 2027
• Last Updated: February 9, 2026
• Results First Posted: February 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (7)