Trial Information

Safety, Biological and Clinical Efficacy of Two Intensity Levels of Theralux Extracorporeal Photochemotherapy in Subjects With Extensive Chronic GvHD Refractory or Intolerant to Standard Therapy: A Randomized, Open-Label Phase I/II Clinical Trial

Graft versus host disease (GvHD) remains a major cause of morbidity and mortality related to
allogeneic stem cell transplantation. While improvements in immuno-suppressive regimens have
reduced the frequency and severity of acute GvHD, the incidence of chronic GvHD (cGvHD)
remains unchanged ranging from 30% after sibling matched related donor transplants to over
70% after unrelated donor bone marrow or peripheral blood stem cell transplant. Factors
associated with cGvHD include increased donor and recipient age, prior acute GvHD, and the
use of alloimmune female donors. Conventional therapeutic approaches for cGvHD, including
corticosteroids and immunosuppressive agents, have demonstrated limited efficacy in patients
with extensive disease and are associated with high toxicity.

Iterative extracorporeal photopheresis has demonstrated clinical and immunomodulatory
activity in subjects with acute and chronic GvHD. The currently available process of ECP has
not been controlled for cell number, exposure time, or specific cell populations targeted
due to the nature of the procedure. Using the Theralux procedure, defined populations of
cells may be targeted, and the intensity of photoactivating agent and exposure can be
modulated to achieve the maximal immunomodulatory effects in the treated subjects. This
study will attempt to explore the effects of the Theralux procedure under two defined
conditions. Response and toxicity will be determined at each intensity level and the dose
associated with clinical response and immunomodulatory effects on DC and NK cell populations
will be defined as the optimal intensity level for subsequent larger trials.