CLINICAL TRIAL: CAT-8015 IN PATIENTS WITH RELAPSED OR REFRACTORY HAIRY CELL LEUK

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hairy cell leukemia (HCL) is a rare lymphoproliferative malignancy accounting for approximately 2% of all leukemias. Standard treatment is a single course of 2-chlorodeoxyadenosine (2-CdA) with complete or partial remission rates of 70%. Response rates after retreatment with 2-CdA are similar but less durable. Repetitive administration carries risks including immunosuppression, marrow aplasia, prolonged cytopenias, infections and neurotoxicity. HCL cells express high levels of CD22. The investigational agent used in this study, CAT-8015, is a recombinant, disulfide-stabilized Fv of the murine monoclonal antibody anti-CD22 antibody, RFB4, fused to a truncated form of pseudomonas exotoxin, PE38. CAT-8015 binds to CD22 and the complex is internalized by endocytosis. The exotoxin domain is translocated to the cytosol where it catalyzes the ADP ribosylation of elongation factor 2, resulting in cell death. CAT-8015 has not been previously studied in humans, but a similar antibody conjugate, CAT-3888 has demonstrated significant activity in clinical studies of relapsed, refractory HCL. CAT-8015 was designed to have greater binding affinity for CD-22 than CAT-3888. The primary objective of this study is to identify the dose-limiting toxicity and maximum tolerated dose of CAT-8015 in patients with relapsed or refractory HCL. Safety, efficacy, pharmacokinetics and immunogenicity of CAT-8015 will be profiled. Although HCL is an indolent disease, all patients in this study will have advanced disease that has failed standard chemotherapy and will have medical indications for treatment of progressive disease.