Blood and Marrow Transplant Clinical Research Network

描述（由申请人提供）：此资助申请旨在更新我们作为核心临床中心和血液和骨髓移植临床试验网络（BMT CTN）指导委员会成员的地位。在过去的35年里，City of Hope造血细胞移植计划一直致力于I、II和III期临床试验的发展，以改善造血细胞移植（HCT）治疗恶性血液病的效果。除了开发基于实验室的转化研究试验外，我们的项目还在减少复发、移植物抗宿主病和CMV感染等领域进行了前瞻性临床试验。在我们作为BMT CTN成员的10年中，我们参与了专注于HCT患者面临的重要问题的临床试验的开发，其中一些来自我们项目中进行的早期研究。骨髓增生异常是一种无法治愈的血液系统恶性肿瘤，在延长无进展生存期方面取得的进展有限。从历史上看，同种异体移植是唯一的治疗方法，但通常仅限于适合完全消融性同种异体移植的年轻患者。鉴于绝大多数MDS患者超过60岁，治疗选择主要是姑息性的。随着低强度预处理（RIC）同种异体HCT的出现，包括我们自己在内的许多中心都开展了针对老年患者骨髓增生异常问题的试验。在我们自己和其他机构进行的II期试验表明，60多岁的患者有机会通过RIC获得潜在的治疗方法。我们建议BMT CTN，一项生物学分配的III期试验，在60岁以上IPSS评分高的患者中比较低甲基化治疗与降低强度同种异体移植。所有患者将接受相同的氮杂胞苷或地西他滨诱导治疗，同时在家族中或通过无关供体登记处进行供体搜索。那些有同种异体捐赠者的患者将继续进行移植，而那些没有捐赠者的患者将继续进行低甲基化治疗，直到白血病进展或发展。这项试验将有助于确定异基因移植在治疗MDS中的作用，并描述这一独特患者人群的短期和长期并发症。患者和医疗保险公司将从这项试验中受益，享受医疗保险福利的患者将有资格参加。该提案代表了BMT CTN的一项国家努力，旨在将骨髓移植治疗MDS的范围扩大到那些没有其他治疗选择的老年患者。作为血液和骨髓移植临床试验网络的一部分，希望之城计划继续领导前瞻性临床试验的开发和执行，以解决造血细胞移植的关键问题。我们还提出了一项全国性试验，以确定降低强度同种异体移植治疗老年高危骨髓增生异常患者的疗效，与现代低甲基化治疗氮杂胞苷或地西他滨相比。这项研究解决了一个重要的卫生保健问题，特别是对于那些进入70岁的没有其他治疗选择的患者。

DESCRIPTION (provided by applicant): This grant application seeks to renew our status as a Core Clinical Center and member of the Steering Committee of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The City of Hope Hematopoietic Cell Transplantation Program has focused its efforts over the last 35 years on the development of Phase I, II and III clinical trials leading to Improvements in hematopoietic cell transplantation (HCT) for the treatment of hematologic malignancy. In addition to developing laboratory-based translational research trials, our program has conducted prospective clinical trials in areas such as reduction of relapse, graft-versus-host disease and CMV infection. During our 10 years as a member of the BMT CTN, we have participated in the development of clinical trials focused on important questions confronting HCT patients, several of which were derived from early phase studies conducted in our program. Myelodysplasia is an incurable hematologic malignancy for which limited progress has been made in extending progression-free survival. Historically, allogeneic transplantation has been the only curative approach, but was generally restricted to younger patients eligible for fully ablative allogeneic transplantation. Given that the vast majority of MDS patients are over 60, treatment options have been primarily palliative. With the advent of reduced intensity conditioning (RIC) allogeneic HCT, many centers, including our own, have developed trials focused on addressing the problem of myelodysplasia in older patients. Phase II trials conducted at our own and other institutions suggest that patients into their 60's have the opportunity for a potential curative approach through RIC. We propose to the BMT CTN, a biologically allocated Phase III trial comparing hypomethylating therapy versus reduced intensity allogeneic transplantation in patients over the age of 60 with high IPSS scores. All patients will receive the same induction therapy with either azacytidine or decitabine, while a donor search, either in the family or through unrelated donor registries, is pursued. Those patients with an allogeneic donor will proceed to transplantation, while those without a donor will continue on with hypomethylating therapy until progression or development of leukemia. This trial will help define the role of allogeneic transplantation in curing MDS, and characterize the short- and long-term complications in this unique patient population. Patients as well as health care underwriters would benefit from this trial, and patients with Medicare benefits would be eligible for participation. This proposal represents a national effort on behalf of the BMT CTN to extend transplantation for treatment of MDS to those older patients with no other curative options. RELEVANCE City of Hope, as part of the Blood and Marrow Transplant Clinical Trials Network, proposes to continue leadership in the development and execution of prospective clinical trials addressing key issues in hematopoietic cell transplantation. We also propose a national trial to determine the efficacy of reduced intensity allogeneic transplantation in curing older patients with high risk myelodysplasia, in comparison to modern hypomethylating therapy with azacytidine or decitabine. This study addresses an important health care issue, particularly for patients entering the seventh decade of life who have no other curative options.