This study will examine the safety and effectiveness of extracorporeal photopheresis (ECP)
for treating chronic graft-versus-host disease (GvHD). GvHD is a common complication of stem
cell transplantation using donated stem cells. It occurs when the donor's T-lymphocytes (a
type of immune cell) see the patient's cells as foreign and mount an immune response to
reject them. The attack can cause skin rash, mouth sores, liver or lung inflammation, lack
of appetite, and muscle stiffness. Chronic GvHD can cause serious illness, and even death,
from the long-term effects of immune dysfunction and from toxic effects of medications (such
as cyclosporine and prednisone) used to treat it.
ECP is an experimental treatment designed to stop the lymphocytes from attacking the body.
It involves collecting some of the cells that cause GvHD, treating them with a combination
of drug and light therapy and returning them to the body. Sixty to 80 percent of patients
with chronic GvHD improve with ECP treatment, and some patients can stop treatment with
prednisone or cyclosporine, or reduce the drug dosages.
Patients with chronic GvHD whose condition has not improved after a minimum 14-day course of
cyclosporine and prednisone may be eligible for this study. Patients must be able to travel
to the NIH Clinical Center in Bethesda, Maryland, twice a week during the 3-month study
Upon entering the study, participants will have a baseline evaluation to measure the extent
of GvHD. This assessment includes blood tests, eye and dental examinations, skin biopsy for
patients with skin involvement, and CT scans and lung function tests to look for possible
lung involvement. Biopsies of the lung, liver, mouth, or eye may be requested if needed to
confirm GvHD in these tissues. The skin will be photographed before starting ECP treatment
and once a month during the treatment period. Following baseline tests, participants will
undergo treatment and evaluations as follows:
Patients will have blood drawn to collect lymphocytes causing GvHD. This may be done with a
special needle or catheter (tube inserted into a vein) or for patients who need or prefer it
with a temporary central venous catheter similar to that used for the stem cell
transplantation. Patients will have three 2- to 3-hour treatments a week for the first week
and two treatments a week after that for a total of 25 treatments over 3 months. Patients
who do not tolerate the treatment...
This is a phase 2 study of extracorporeal photopheresis (ECP) for treatment of chronic graft
versus host disease following allogeneic hematopoietic stem cell transplantation.
Extracorporeal exposure of human mononuclear cells to ultraviolet A radiation following
photosensitization with 8-methoxypsoralen has proven to be an effective treatment for
cutaneous T-cell lymphoma. Small, single institution studies have suggested efficacy in
other T-cell mediated diseases such as solid organ rejection and graft versus host disease.
This a phase 2 study of ECP for treatment of chronic graft versus host disease. Eligible
patients must have objective evidence of chronic graft versus host disease that is
refractory to conventional therapy or must have steroid-dependent disease that does not
permit steroid dose reduction. The primary objective of this study is to better define the
safety, efficacy and mechanism of action of ECP for treatment of patients with chronic graft
versus host disease.
- INCLUSION CRITERIA:
1. Objective evidence of chronic graft versus host disease involving the skin,
lungs, gastrointestinal tract, liver, or eyes.
2. Progressive or stable GvHD despite a minimum of 30 days treatment with a
calcineurin inhibitor (cyclosporine or tacrolimus) at therapeutic plasma levels,
plus at least one other another agent with a different mechanism of action used
concurrently for at least 30 days at doses known to be therapeutic for cGvHD. In
most cases this second agent will be a corticosteroid administered either as
high level pulse dosing (greater than or equal to mg/kg/day prednisone or
equivalent in pulses of 3 days or longer for at least two occasions during the
qualifying 30 days) and/or daily dosing (greater than or equal to 0.25mg/kg) or
alternate day dosing (greater than or equal to 0.50 mg/kg) prednisone or
equivalent. In other cases where use of steroids is medically undesirable or
contraindicated, the second agent may be mycophenolate mofetil, sirolimus,
hydroxychloroquine, clofazimine, thalidomide, azathioprine, pentostatin,
etanercept, Infliximab, Rituximab or Daclizumab used at doses and schedule known
to provide benefit to patients with cGvHD. Patients in whom calcineurin
inhibitors are medically contraindicated may also be eligible for enrollment if
there has been at least a 30 day trial of prednisone (or equivalent) at the
doses/schedules noted above plus one of the second agents listed above. Patients
in whom both calcineurin inhibitors and steroids are medically contraindicated
or in whom these agents can be used at only limiting doses may also be eligible
if at least two of the alternate agents noted above have been tried for 30 days
without further improvement in symptoms of cGvHD. Patients who have
stabilization of disease on calcineurin inhibitors plus steroids (or the other
combinations noted above), but in whom these medications cannot be tapered
without disease flare are also eligible.
3. Adequate (as determined by PI) renal, hepatic, and cardiac reserve to enable the
patient to tolerate Extracorporeal Photopheresis.
4. The patient's malignancy (if applicable) is in complete remission or the patient
is not a candidate for further immune-based anti-tumor therapy (such as donor
lymphocyte infusions or immunomodulatory cytokines) due to severity of GvHD.
5. WBC greater than or equal to 1000 and platelets greater than or equal to 25,000.
6. Weight greater than or equal to 30kg.
7. Female patients not pregnant and agree to use a reliable method of birth control
during the treatment period
8. Systolic blood pressure greater than or equal to 90 mm Hg.
9. Karnofsky score or Lansky score greater than or equal to 30.
10. Predicted life expectancy of at least 3 months.
11. A minimum of 100 days following stem cell transplantation.
12. A minimum of 30 days without a response to, and 7 days following cessation of,
certain investigational 2nd-line agents for treatment of GvHD (specifically:
thalidomide, azathioprine, pentostatin, etanercept, Infliximab, Rituximab or
13. History of failure to achieve any clinical benefit from a previous treatment
with ECP where at least 3 months (12 weeks) of twice a week every other week
therapy was administered.
14. Signed and witnessed informed consent.
15. Hemoglobin greater than 9.5, hematocrit greater than 28.5 (patients not meeting
this inclusion criterion may be treated with iron supplementation and/or
erythropoietin/darbepoetin until their hgb/hct are in the Inclusion range and
may then be reconsidered for study entry).
1. Hypersensitivity or allergy to psoralen (methoxypsoralen).
2. Hypersensitivity to both heparin and/or citrate products.
3. Patients who are unable to visit the NIH clinical center twice a week for at least
the first four week treatment period of ECP treatments; or for the NIH or arranged
home treatments with ECP thereafter; or for the every 4 week medical evaluation
visits to NIH.
4. Frank gastrointestinal bleeding due to GvHD (occult blood positivity excluded).
5. Patients taking a cancer chemotherapeutic agent for continued treatment of
6. Patients undergoing radiation therapy.
7. The patient's malignancy (if applicable) is NOT in complete remission or the patient
is a candidate for further immune-based anti-tumor therapy (such as donor lymphocyte
infusions or immunomodulatory cytokines) to treat GvHD.