Amotosalen PCT of Leukapheresis Units for GvHD Therapy

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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.