Amotosalen PCT of Leukapheresis Units for GvHD Therapy

这是一个合并的阶段I/！1 SBIR快速通道提案。骨髓移植是一种 提供血液恶性肿瘤的疾病症状的完全治愈的潜力，并且最终， 有适当的安全性，血红蛋白病的症状也是如此。即使在相关的情况下， 完全匹配的骨髓移植，有发病率和死亡率与移植物抗- 宿主病（GvHD）。成功应用不匹配（相关-单倍体相合和无关）骨 对白血病或淋巴瘤患者进行骨髓移植需要改善患者的总体结局， 获得BMT，再加上避免或成功治疗目前经历的GvHD， 现有的不匹配的骨髓移植（BMT）方案。这两个目标可能需要使用 低强度预处理（RIC）方案，以支持移植。体外 光采（ECP）已被证明是移植后GvHD的有效治疗方式 并且作为治疗方案越来越受欢迎。这一SBIR提案旨在制定一项 更简单和更便宜的方法， 自体白细胞，这将有助于确定所需的光化学处理细胞的治疗剂量 对于等同于使用当前获批ECP观察到的临床反应 仪器和协议。本申请的第一阶段将建立体外光化学给药 以及向FDA成功申请IND所需的监管验证 ECP版本。II期将支持临床试验，作为本方案获得监管批准的第一步 和产品。I期临床试验将是塔夫茨新英格兰医学中心的一项单一研究者试验。 中心，Francine Foss博士为研究的首席研究员。Cerus公司是世界领先的 光化学在临床上的应用。我们最近完成了一项研究， 支持美国公共卫生服务基金R 01 HL 63456，“干细胞移植建立 异源嵌合体。“此外，我们还参与了三项使用盐酸氨托沙林的临床试验。 用于骨髓移植和作为EB病毒疫苗的光化学处理的白细胞 病毒

This is a combined Phase I/!1 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.