Protocol Number: 03-I-0025

Title:

Treatment of Chronic Graft Versus Host Disease with Extracorporeal Photopheresis

Number:

03-I-0025

Summary:

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 period.

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:

ECP Treatment

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 or develop complications will stop treatment early, and patients who may benefit from treatment beyond 3 months may continue therapy for longer.

Evaluations

Patients will be evaluated for response to therapy once a month with the following tests and procedures:

-Patients with skin or mouth involvement will have a skin evaluation by a dermatologist and photographs of the entire body taken by a medical photographer.

-Patients with eye involvement will have an eye examination.

-Patients with muscle or joint involvement will have physical therapy.

After completing therapy, patients will have follow-up evaluations every 6 months for 2 years. Those with lung involvement will have CT scans and lung function tests during these visits.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

a. Objective evidence of chronic graft versus host disease involving the skin, lungs, gastrointestinal tract, liver, or eyes.

b. 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.

c. Adequate (as determined by PI) renal, hepatic, and cardiac reserve to enable the patient to tolerate Extracorporeal Photopheresis.

d. 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.

e. WBC greater than or equal to 1000 and platelets greater than or equal to 25,000.

f. Weight greater than or equal to 30kg.

g. Female patients not pregnant and agree to use a reliable method of birth control during the treatment period

h. Systolic blood pressure greater than or equal to 90 mm Hg.

i. Karnofsky score or Lansky score greater than or equal to 30.

j. Predicted life expectancy of at least 3 months.

k. A minimum of 100 days following stem cell transplantation.

l. 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 Daclizumab).

m. 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.

n. Signed and witnessed informed consent.

o. 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).

EXCLUSION CRITERIA:

a. Hypersensitivity or allergy to psoralen (methoxypsoralen).

b. Hypersensitivity to both heparin and/or citrate products.

c. 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.

d. Frank gastrointestinal bleeding due to GvHD (occult blood positivity excluded).

e. Patients taking a cancer chemotherapeutic agent for continued treatment of malignancy.

f. Patients undergoing radiation therapy.

g. 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.

Special Instructions:

Currently Not Provided

Keywords:

Psoralen

Refractory

Transplantation

Stem Cell

UVA

Recruitment Keyword(s):

Transplantation

Graft-versus-host Disease

GVHD

Condition(s):

Graft vs Host Disease

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Procedure/Surgery: Extracorporeal Photopheresis

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Akpek G, Zahurak ML, Piantadosi S, Margolis J, Doherty J, Davidson R, Vogelsang GB. Development of a prognostic model for grading chronic graft-versus-host disease. Blood. 2001 Mar 1;97(5):1219-26.

Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE, Appelbaum FR, Doney KC, Weiden P, Anasetti C, et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood. 1988 Aug;72(2):555-61.

Yoo EK, Rook AH, Elenitsas R, Gasparro FP, Vowels BR. Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell Lymphoma: relevance to mechanism of therapeutic action. J Invest Dermatol. 1996 Aug;107(2):235-42.

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