Towards Effective, Patient-tailored Anti-plasma Cell Therapies in AL Amyloidosis: Predicting Drug Response and Overcoming Drug Resistance
2026年5月7日 更新者：Mario Nuvolone、Fondazione IRCCS Policlinico San Matteo di Pavia
Through an observational clinical study, partly prospective and partly retrospective, based on the collection of clinical data and on in vitro experimental analyses carried out on residual biological samples obtained during routine clinical procedures, it is proposed to identify predictive biomarkers of in vivo response to first-line therapies.
研究概览
地位
完全的
条件
研究类型
观察性的
注册 (实际的)
250
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
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Lombardy
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Pavia、Lombardy、意大利、27100
- Fondazione IRCCS Policlinico San Matteo
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
取样方法
非概率样本
研究人群
Newly diagnosed, treatment naïve AL amyloidosis patients with non-IgM plasma cell clones, evaluated at the amyloidosis Research and Treatment Center of Pavia, undergoing a diagnostic bone marrow aspiration will be enrolled.
描述
Inclusion Criteria:
- Biopsy-proven systemic AL amyloidosis
- No IgM clone
- No history of anti-plasma cell therapy
- Diagnostic bone marrow aspiration at ARTC
- Age > 18 years
- Willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes through signing a written informed consent.
Exclusion Criteria:
- Non-AL amyloidosis
- IgM clone
- Previous anti-plasma cell therapy
- Age <18 years
- Failure to show willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Identification of predictive biomarkers of response to proteasome inhibitor-based first-line therapy in AL amyloidosis
大体时间：From baseline (diagnosis) to 6 months after initiation of first-line therapy
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To identify and validate biological, genetic, and proteomic biomarkers predictive of in vivo response to proteasome inhibitor-based first-line therapies in patients with AL amyloidosis.
This will be achieved through the integration of ex vivo drug sensitivity assays performed on patient-derived CD138+ plasma cells, characterization of plasma cell and mesenchymal stromal cell biological features, and retrospective and prospective molecular analyses.
Biomarker profiles will be correlated with hematologic response at 6 months and used to develop a predictive statistical model of treatment response.
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From baseline (diagnosis) to 6 months after initiation of first-line therapy
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Molecular characterization of mechanisms of resistance to proteasome inhibitors
大体时间：From baseline (diagnosis) to MRD assessment after achievement of complete hematologic response (approximately up to 12-24 months)
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To investigate the mutational, transcriptional, and proteomic profiles associated with in vivo resistance to proteasome inhibitors by comparing plasma cell clones at diagnosis and minimal residual disease (MRD).
Analyses will include next-generation sequencing, targeted DNA sequencing of genes involved in proteostasis, and quantitative proteomics to identify molecular determinants of drug resistance.
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From baseline (diagnosis) to MRD assessment after achievement of complete hematologic response (approximately up to 12-24 months)
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Evaluation of the therapeutic potential of deubiquitinating enzyme (DUB) inhibitors
大体时间：At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
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To assess the ex vivo sensitivity of patient-derived amyloidogenic plasma cells to DUB inhibitors and to characterize the expression of DUB family members at RNA and protein level.
The study will evaluate whether DUB inhibition can overcome resistance to proteasome inhibitors and identify candidate DUB inhibitors for therapeutic development.
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At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
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Role of mesenchymal stromal cells in modulating drug response
大体时间：At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
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To evaluate the contribution of patient-derived mesenchymal stromal cells to resistance against proteasome inhibitors by assessing their protective effect in co-culture systems with amyloidogenic plasma cells or cell lines.
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At baseline (sample collection at diagnosis) and during ex vivo experimental analyses
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2022年1月13日
初级完成 (实际的)
2026年3月30日
研究完成 (实际的)
2026年3月30日
研究注册日期
首次提交
2026年5月7日
首先提交符合 QC 标准的
2026年5月7日
首次发布 (实际的)
2026年5月13日
研究记录更新
最后更新发布 (实际的)
2026年5月13日
上次提交的符合 QC 标准的更新
2026年5月7日
最后验证
2026年5月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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