Amotosalen PCT of Leukapheresis Units for GvHD Therapy

描述（由申请人提供）：这是一个合并的I/II期SBIR快速通道提案。骨髓移植具有完全治愈恶性血液病症状的潜力，并且最终具有适当的安全性，也可以治愈血红蛋白病的症状。即使在相关的完全匹配骨髓移植的情况下，也存在与移植物抗宿主病（GvHD）相关的发病率和死亡率。对白血病或淋巴瘤患者成功应用错配（相关-单倍体相同和不相关）骨髓移植需要获得更好的BMT总体结果，同时避免或成功治疗目前在现有的错配骨髓移植（BMT）方案中经历的GvHD。这两个目标可能需要使用低强度调节（RIC）方案来支持移植。体外光移植术（Extracorporeal Photopheresis， ECP）已被证明是移植后GvHD的有效治疗方式，并且作为一种治疗方案越来越受欢迎。这项SBIR提案旨在开发一种更简单、更便宜的方法，用于对移植患者的自体白细胞进行补骨脂素光化学治疗，这将有助于确定光化学治疗细胞的治疗剂量，以达到与使用目前批准的ECP仪器和方案观察到的临床反应相当的效果。该申请的第一阶段将建立体外光化学剂量和监管验证，这将是成功向FDA申请新版ECP的IND所必需的。II期将支持临床试验，作为监管部门批准该方案和产品的第一步。一期临床试验将在塔夫茨-新英格兰医学中心进行，由Francine Foss博士担任该研究的首席研究员。Cerus公司是补骨脂素光化学在临床应用领域的全球领导者。我们最近在美国公共卫生服务基金R01 HL63456的支持下完成了一项研究，“干细胞移植建立同种嵌合”。此外，我们还参与了三项临床试验，利用Amotosalen-HCI光化学处理的白细胞用于骨髓移植和作为爱泼斯坦-巴尔病毒的疫苗。

DESCRIPTION (provided by applicant): This is a combined Phase I/II SBIR Fast-Track proposal. Bone marrow transplantation has the potential of providing a complete cure of the disease symptoms of hematologic malignancies and, ultimately, with an appropriate safety profile, the symptoms of hemoglobinopathies as well. Even in the case of related fully matched bone marrow transplantation, there is morbidity and mortality associated with Graft-versus- Host-Disease (GvHD). Successful application of mismatched (related-haploidentical and unrelated) Bone Marrow Transplantation to patients with leukemia or lymphoma requires that improved overall outcomes of the BMT be obtained, coupled with the avoidance or successful treatment for the GvHD now experienced in existing mismatched bone marrow transplantation (BMT) protocols. These two goals may require use of reduced-intensity conditioning (RIC) regimens in support of the transplantation. Extracorporeal Photopheresis (ECP) has proved to be effective as a treatment modality for GvHD following transplantation and is gaining popularity as a treatment protocol. This SBIR proposal is directed at the development of a more simple and less expensive process for the psoralen photochemical treatment of the transplant patient's autologous leukocytes which will help define the therapeutic dose of photochemically treated cells required for clinical responses equivalent to those which have been observed using present approved ECP instrumentation and protocols. Phase I of this application will establish the in vitro photochemical dosing and the regulatory validations, which will be required for a successful IND application to the FDA for this new version of ECP. Phase II will support a clinical trial as a first step toward regulatory approval of this protocol and product. The Phase I Clinical Trial will be a single investigator trial at the Tufts-New England Medical Center with Dr. Francine Foss as the Lead Investigator of the study. Cerus Corporation is the world's leader in the application of psoralen photochemistry in the clinic. We have recently completed a study through the support of US Public Health Service Grant R01 HL63456, "Stem Cell Transplantation to Establish Allochimerism." In addition we are associated with three clinical trials utilizing Amotosalen-HCI photochemically treated leukocytes for use in bone marrow transplantation and as a vaccine for Epstein-Barr virus.