A Randomized Placebo-Controlled Phase 2 Study of Metformin for the Prevention of Progression of Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma
概览
- 阶段
- 2 期
- 干预措施
- Metformin XR
- 疾病 / 适应症
- Monoclonal Gammopathy of Undetermined Significance
- 发起方
- Dana-Farber Cancer Institute
- 入组人数
- 60
- 试验地点
- 7
- 主要终点
- (M-)Protein Concentrations Change
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
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)
详细描述
This is a Phase 2, double-blind, randomized placebo-controlled trial in patients with higher-risk monoclonal gammopathy of undetermined significance (MGUS) and low-risk smoldering multiple myeloma (SMM) to test the efficacy of metformin in reducing clinical indicators of disease progression in MGUS and SMM patients. Metformin is considered "investigational", which means it has not been approved for the study of cancer prevention by the United States Food and Drug Administration. It has been approved for other uses including for blood sugar control in some people with Type II diabetes. Multiple myeloma is a cancer of the plasma cells, which is an important part of the immune system. Patients with active multiple myeloma generally require treatment. There are currently no approved therapies for MGUS and SMM patients. Metformin is a medication that is commonly used in the treatment of diabetes. Metformin works by decreasing glucose production in the liver, decreasing glucose absorption, and improving insulin sensitivity. This study is interested in studying this medication because several recent studies indicate that the drug may help prevent progression in patients with MGUS or SMM. This study is looking to learn more about whether metformin will benefit patients with MGUS or SMM who may not have diabetes. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. After enrollment participants will be randomized assigned to receive either the Placebo or Metformin pills and to take them for 6 months depending on participant tolerance to the drug. Participants will have the option to learn their treatment assignment after primary (6-month) outcome assessments are complete, and individuals randomized to metformin will have the opportunity to continue to take metformin for an additional 6-months to allow for the observation of potentially longer-term treatment response. Participants who choose to be unblinded and are taking placebo will discontinue study medication. It is expected that about 80 people will take part in this research study. The National Cancer Institute of the National Institutes of Health is supporting this trial.
研究者
Omar Nadeem, MD
Principal Investigator
Dana-Farber Cancer Institute
入排标准
入选标准
- •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).
- •Low-Risk Smoldering Myeloma: bone marrow plasma cells ≥10%# with the absence of additional high-risk features, which are further defined in the
排除标准
- •#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%
- •Serum involved/uninvolved FLC ratio ≥100, provided the absolute level of the involved free light chain is at least 100 mg/L and repeated twice (light chain smoldering myeloma as described in section 2.4 is not an exclusion criteria).
- •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
研究组 & 干预措施
Metformin
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 )
干预措施: Metformin XR
Placebo
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.
干预措施: Placebo
结局指标
主要结局
(M-)Protein Concentrations Change
时间窗: Baseline to 6-months
Assessed by using the serum-protein electrophoresis
次要结局
- Changes in PROMIS Global Health Summary Score v1.2(Baseline to 6-months)
- Molecular Evolution of Immune Cells (CD138- or CD45+)(Baseline to 6-months)
- 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)
- Changes in Plasma Metabolites Measured by Liquid Chromatography-mass Spectrometry(Baseline to 6-months)
- Number of Participants Willing to Continue to Take Metformin Beyond 6 Month Primary Assessment Period(Baseline- 12 months)
- Changes in Response for Those Who Choose to Take Metformin for up to 1 Year Per IMWG Response Criteria(Baseline- 12 months)