Screening for AL Amyloidosis in Smoldering Multiple Myeloma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 13
- 主要终点
- Creating a network to enroll patients on a collaborative study requiring marrow and blood specimens, to collect data for a training set of likelihood statistics and to plan a future validation study.
研究概览
简要总结
In this multicenter study, we will recruit 400 patients 40 years of age or older at 15 centers with a diagnosis of smoldering multiple myeloma (SMM), a group of patients for whom standard of care is observation not treatment. The main goal of this study is to screen for the diagnosis of light-chain amyloidosis (AL) before the onset of symptomatic disease and to develop a training set for a likelihood algorithm.
详细描述
This study is based on results from two prior studies in which 4 of 36 patients with SMM and none of 14 patients with MGUS were found to have AL. The hypothesis that we test with this protocol is that patients with (1) a pre-existing diagnosis of SMM, (2) free light chain (FLC) abnormalities, (3) IGLV genes associated with AL,(4) t(11;14) or gain 1q, and (5) NT-proBNP > 332pg/mL will have undiagnosed AL or risk of progression to AL. We will study the potential for SMM, the FLC screen, AL-related IGLV gene use, t(11;14) or gain 1q cytogenetic abnormalities, and NT-proBNP > 332pg/mL to be the variables in a likelihood algorithm for AL.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 40 years of age and older
- •diagnosed with either Smoldering Multiple Myeloma or a Monoclonal Gammopathy
- •dFLC greater than 23 mg/L
- •abnormal FLC ratio
- •If the patient has an eGFR less than 50 mL/min/1.73m2, the FLC ratio is inconsequential. The patient only needs to meet the age and dFLC criterion.
排除标准
- •Patients younger than 40 years of age are not eligible
- •Patients with a previous finding of amyloid in other biopsies will not be included
- •Adults unable to consent are not eligible, including the cognitively impaired Pregnant women, pregnant minors, minors (i.e., individuals who are not yet adults), wards of the state, non-viable neonates, neonates of uncertain viability, and prisoners are not eligible
结局指标
主要结局
Creating a network to enroll patients on a collaborative study requiring marrow and blood specimens, to collect data for a training set of likelihood statistics and to plan a future validation study.
时间窗: 5 years
With a 15-center network covering 12 states and almost 45% of the US population, we will evaluate 400 SMM patients \> 40 years old who pass FLC criteria using standard of care tests including NT-proBNP and clinical marrow specimens evaluated for the presence of t(11;14) and gain1q. Marrow cells will be processed by NGS for clonal IGLV gene identification. With the training data obtained, we will use existing statistical modeling techniques to generate a statistical algorithm for identifying undiagnosed cases of AL and assessment of risk of AL, and to plan a validation study testing the training model. We will also investigate a role for the novel biomarker clusterin (Clu) as an indicator of risk of AL in SMM patients; preliminary work indicates that Clu is significantly lower in AL than in SMM patients.
Validating an NGS assay that identifies IGLV genes in clonal plasma cells
时间窗: 5 years
All subjects will have their clonal IGLV genes identified by NGS enabling the creation and validation of a laboratory developed test in a precision medicine laboratory that is certified under regulations of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Approval for this laboratory developed test for both κ and λ IGVL genes will permit providers, patients and researchers to use the test in decision-making to care for monoclonal gammopathy patients. We will also investigate the exploratory objective of defining the alterations in sequence in AL and non-AL FLC derived from the same IGLV germline gene.
次要结局
未报告次要终点