Ancillary Studies in Clinical Trials - PRIMeR

描述（申请人提供）：STaMINA（干细胞移植用于多种骨髓瘤治疗新药）临床试验是一项随机、多中心、III期研究，评估标准自体造血细胞移植（autoHCT）后的3种不同治疗：1）第二次autoHCT，随后3年来那度胺维持，2）仅3年来那度胺维持，3）4个周期的化疗，包括来那度胺（Revlimid（r）），硼替佐米（Velcade（r））和地塞米松（RVD），随后是3年的来那度胺维持。这项试验将从大约50个美国移植中心招募750名患者，并于2010年6月开始招募。PRIMeR（骨髓瘤反应的免疫表型诊断）辅助研究将使用浆细胞标志物的综合7色面板来区分2010年12月至2013年6月入组STaMINA临床试验的约470名患者的正常和异常（骨髓瘤）浆细胞。到目前为止，没有研究评价了在比较不同治疗策略的大型临床试验中通过免疫表型检测到的微小残留病，也没有在接受新型药物治疗的患者中进行免疫表型研究的报道。在诸如影响免疫蛋白产生的autoHCT的治疗之后，使用标准疾病测试检测少量残留疾病（骨髓瘤）的能力不太精确。免疫分型可以补充或取代标准测试，因为它直接测量异常（骨髓瘤）浆细胞的数量，而不是测量异常浆细胞分泌的异常蛋白质的量。免疫分型是一种成本效益高的方法，可以在10，000个正常浆细胞中检测到1个异常浆细胞，灵敏度为0.01%。随着现代骨髓瘤治疗后完全缓解率的增加，越来越需要对疾病反应性进行更敏感的评估，并随着时间的推移监测疾病负担。PRIMeR研究的总体目的是在入组STaMINA试验的骨髓瘤患者中使用免疫表型分析来测量微小残留病，以确定微小残留病与标准骨髓瘤检测的相关性及其预测长期生存结局的能力。一旦STaMINA临床试验数据成熟，PRIMeR研究将进行生存分析，以确定免疫表型在新型药物和autoHCT时代的预后价值。PRIMeR研究有可能通过提供免疫分型预测长期生存和指导治疗决策的能力的证据来改变临床实践。此外，微小残留病可作为临床试验的替代终点，从而加速未来治疗的发展。公共卫生部门：该项目将比较在BMT CTN STaMINA临床试验中接受三种不同治疗的多发性骨髓瘤患者的微小残留病检测。本研究的结果将提高疾病评估的质量，并在多发性骨髓瘤中建立一个强大的替代标志物。(End摘要）

DESCRIPTION (provided by applicant): The STaMINA (Stem cell Transplant for multiple Myeloma Incorporating Novel Agents) clinical trial is a randomized, multi-center, phase III study evaluating 3 different treatments after a standard autologous hematopoietic cell transplant (autoHCT): 1) a second autoHCT followed by 3 years of lenalidomide maintenance, 2) 3 years of lenalidomide maintenance only, 3) 4 cycles of chemotherapy including lenalidomide (Revlimid(r)), bortezomib (Velcade(r)), and dexamethasone (RVD) followed by 3 years of lenalidomide maintenance. This trial will enroll 750 patients from about 50 U.S. transplant centers and started accrual in June of 2010. The PRIMeR (PRognostic Immunophenotyping in Myeloma Response) ancillary study will use a comprehensive 7-color panel of plasma cell markers to differentiate between normal and abnormal (myeloma) plasma cells in about 470 patients who are enrolled in the STaMINA clinical trial from December 2010 to June 2013. To date, no studies have evaluated minimal residual disease detected by immunophenotyping in a large clinical trial comparing different treatment strategies, and no immunophenotyping studies have been reported in patients treated with novel agents. After treatments such as autoHCT which affect the production of immune proteins, the ability to detect small amounts of residual disease (myeloma) using standard disease tests is less precise. Immunophenotyping may complement or replace standard testing since it directly measures the number of abnormal (myeloma) plasma cells instead of measuring the amount of abnormal proteins secreted by the abnormal plasma cells. Immunophenotyping is a cost-effective method which can detect 1 abnormal plasma cell in 10,000 normal plasma cells, yielding a sensitivity of 0.01%. With the increase in complete response rates after modern myeloma therapy, there is an increasing need for more sensitive evaluations of disease responsiveness and monitoring disease burden over time. The overall purpose of the PRIMeR study is to measure minimal residual disease using immunophenotyping analyses in myeloma patients enrolled in the STaMINA trial to determine the association of minimal residual disease with standard myeloma tests and its ability to predict long-term survival outcomes. The PRIMeR study will perform survival analyses once the STaMINA clinical trial data have matured to determine the prognostic value of immunophenotyping in the era of novel agents and autoHCT. The PRIMeR study has the potential to change clinical practice by providing evidence of the ability of immunophenotyping to predict long-term survival and guide treatment decisions. In addition, minimal residual disease may serve as a surrogate endpoint for clinical trials, thereby speeding the development of future therapies. PUBLIC HEALTH REVELANCE: This project will compare the detection of minimal residual disease in patients with multiple myeloma who receive three different therapies under the BMT CTN STaMINA clinical Trial. The results of this study will improve the quality of disease assessment and establish a powerful surrogate marker in multiple myeloma. (End of Abstract)