背景:当前急性淋巴细胞白血病(ALL)治疗的一个关键挑战是强化治疗,以降低复发风险最高的患者亚组的复发率。为期一年的维持阶段对于预防复发至关重要。硫嘌呤增强ALL维护(TEAM)试验研究了ALL维护的新策略。
方法:TEAM是ALLTogether1试验的随机3期子方案,其中包括0-45岁新诊断的B细胞前体或T细胞ALL患者,并分层到中等风险高(IR高)组,13个欧洲国家在团队审判中,传统的甲氨蝶呤(MTX)/6-巯基嘌呤(6MP)维持骨干(对照臂)补充低剂量(2.5-12.5mg/m2/天)口服6-硫鸟嘌呤(6TG)(实验臂),而6MP的起始剂量从75mg/m2/天减少到50mg/m2/天。在约5年内,共有778名患者将被纳入TEAM。当最后纳入的患者从诱导治疗结束后随访5年时,研究将结束。该研究的主要目的是通过将6TG添加到基于6MP/MTX的维持治疗中来显着改善IR高ALL患者的无病生存率(DFS)。TEAM有80%的能力通过降低50%的复发率来检测5年DFS增加7%。DFS将通过意向治疗分析进行评估。除了减少复发,TEAM还可以减少由高水平的甲基化6MP代谢物引起的肝毒性和低血糖。将监测甲氨蝶呤/6MP代谢物,并将低水平报告给临床医生,以识别潜在的非粘附患者。
结论:TEAM为ALL的维持治疗提供了一种新策略,具有通过降低复发率改善DFS的潜力。已考虑的潜在风险因素包括肝窦阻塞综合征/结节性再生增生,第二癌症,感染,和骨坏死.代谢物监测可以潜在地增加两个治疗组中的治疗依从性。
背景:EudraCT,2018-001795-38。注册2020-05-15,Clinicaltrials.gov,NCT04307576。注册2020-03-13,https://clinicaltrials.gov/ct2/show/NCT04307576。
BACKGROUND: A critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM)
trial investigates a novel strategy for ALL maintenance.
METHODS: TEAM is a randomized phase 3 sub-protocol to the ALLTogether1
trial, which includes patients 0-45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM
trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5-12.5 mg/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 5 years. The
study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the
study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse, TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients.
CONCLUSIONS: TEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms.
BACKGROUND: EudraCT, 2018-001795-38. Registered 2020-05-15, Clinicaltrials.gov , NCT04307576 . Registered 2020-03-13, https://clinicaltrials.gov/ct2/show/NCT04307576.