A Safety and Efficacy Study of Uvadex and Extracorporeal Photopheresis (ECP) in Chronic Graft Versus Host Disease

This is an open-label study (patients and study staff will know the identity of treatments
assigned during the study) in patients with chronic graft-versus-host disease (cGvHD).
Chronic graft-versus-host disease (a donator-versus-recipient-disease) is a complication
that can occur after a blood stem cell or bone marrow transplant with cells from a related
or unrelated donator. During cGvHD, the transplanted cells attack the recipient's body.
Patients with cGVHD who meet entry criteria for the study will be randomly assigned to
receive standard of care treatment for 26 weeks or standard or care treatment with
extracorporeal photopheresis (ECP) for 26 weeks. Standard of care treatment consists of
orally (taken by mouth) administered corticosteroids (drugs that reduce inflammation) and
cyclosporine (CsA)or Tacrolimus ( drugs that suppress the patient's immune response). ECP
therapy is a process that takes place in a device where the investigational drug UVADEX
(methoxsalen) is injected into a germ-free bag mixed with the patient's white blood cells.
After the blood cells have absorbed the drug and are exposed to ultraviolet A (UVA)
radiation, the blood cells are injected back into the patient's body. During the study, a
third party assessor at each study center who will be blinded (will not know) to treatment
will assess the condition each patient's skin and oral mucosa at protocol-specified visits
and will complete a total skin score for all patients . The study will consist of 3 phases:
a screening phase, an open label treatment phase and an end-of-study (or early withdrawal)
phase. The duration of patient participation will be 28 weeks and patient safety will be
monitored throughout the study. An additional non-interventional 2 year follow-up will begin
after the 28 week/withdrawal end-of-study phase.

Inclusion Criteria:

- Have new onset of moderate or severe cGvHD as assessed by the NIH Consensus Criteria
Clinical Assessment (staging and severity) with onset within 2 years of
transplantation (Patients with prior acute GvHD should be on a stable dose of <0.5
mg/kg daily prednisone, or equivalent, for at least 2 weeks prior to study entry.
Prior ECP for patients with acute GvHD is permitted in the study);willing to start
1.0mg/kg prednisone: Be using adequate birth control; If a woman, must have negative
pregnancy test result at screening: Be able and willing to comply with all study
procedures including providing informed consent

- Long term follow up: Enrolled into the primary study and provide written consent

Exclusion Criteria:

- Be intolerant to corticosteroids; Received treatment with >2.0 mg daily prednisone,
or equivalent, for cGvHD for more than 7 days prior to baseline visit; received
treatment with prednisone for mild cGVHD with >.5mg/kg for > 14 days, Have evidence
of known infection with human immunodeficiency virus (HIV), active Hepatitis B
infection, or have uncontrolled infection requiring treatment at the time of study
entry; Requires treatment with budesonide and similar low absorption oral steroids
and steroid enema preparations; Receiving treatment with mycophenolate mofetil
(MMF),PUVA, tyrosine kinase inhibitors, anti-tumor necrosis factor (TNF) agents,
sirolimus, and bortezomib; Receiving treatment with alemtuzumab, antithymocyte
globulin (ATG) or other similar long-acting agents used for treatment of acute or
chronic GvHD or administered during the conditioning regimen <90 days prior to
randomization