Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Acute Graft Versus-Host Disease

Sponsor

Mallinckrodt (Industry)

Overall Status

Terminated

CT.gov ID

NCT00282503

Collaborator

PRA Health Sciences (Industry)

Enrollment

Locations

Arms

0.5

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of ECP treatment combined with high dose corticosteroids versus high dose corticosteroids alone, in the treatment of patients with newly diagnosed acute GvHD (Grades II to III) that developed within 100 days following an allo HPCT.

Condition or Disease	Intervention/Treatment	Phase
Acute Graft-versus-Host Disease	Drug: Methoxsalen+ECP, Methylprednisolone Procedure: Ecp	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Controlled, Parallel-Group, Multicenter Study of Extracorporeal Photoimmune Therapy With THERAKOS* UVADEX* for the Treatment of Patients With Newly Diagnosed Acute Graft Versus-Host Disease

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: methylprednisolone equivalent. 2mg/kg daily will be administered initially and may be tapered according to a tapering schedule provided in the protocol.	Drug: Methoxsalen+ECP, Methylprednisolone Those patients randomized to the ECP Treatment arm will receive ECP treatments by the following regimen: Weeks 1 through Week 3 - 3 times within each week. (Treatments do not have to be performed on consecutive days but should be completed within the 7-day period), Weeks 4 through 12 - 2 times each week. (It is preferable that patients receive ECP treatments on consecutive days within a week, but there should never be > 4 days between the ECP treatments within a week.) Methylprednisolone will be started at 2mg/kg daily dose and may be tapered by reducing dose each week at the following reductions: Daily Dose (mg/kg) 1 1.5 2 1.0 3 0.70 4 0.50 5 0.40 6 0.30 7 0.20 8 0.10 Other Names: Uvadex+ ECP
Experimental: Uvadex+ECP Those patients randomized to the ECP Treatment arm will receive ECP treatments by the following regimen: Weeks 1 through Week 3 - 3 times within each week. (Treatments do not have to be performed on consecutive days but should be completed within the 7-day period), Weeks 4 through 12 - 2 times each week. (It is preferable that patients receive ECP treatments on consecutive days	Drug: Methoxsalen+ECP, Methylprednisolone Those patients randomized to the ECP Treatment arm will receive ECP treatments by the following regimen: Weeks 1 through Week 3 - 3 times within each week. (Treatments do not have to be performed on consecutive days but should be completed within the 7-day period), Weeks 4 through 12 - 2 times each week. (It is preferable that patients receive ECP treatments on consecutive days within a week, but there should never be > 4 days between the ECP treatments within a week.) Methylprednisolone will be started at 2mg/kg daily dose and may be tapered by reducing dose each week at the following reductions: Daily Dose (mg/kg) 1 1.5 2 1.0 3 0.70 4 0.50 5 0.40 6 0.30 7 0.20 8 0.10 Other Names: Uvadex+ ECP Procedure: Ecp ECP or Extra Corporeal Phototherapy will be used with UVADex

Arm

Intervention/Treatment

Active Comparator: methylprednisolone equivalent.

2mg/kg daily will be administered initially and may be tapered according to a tapering schedule provided in the protocol.

Drug: Methoxsalen+ECP, Methylprednisolone

Those patients randomized to the ECP Treatment arm will receive ECP treatments by the following regimen: Weeks 1 through Week 3 - 3 times within each week. (Treatments do not have to be performed on consecutive days but should be completed within the 7-day period), Weeks 4 through 12 - 2 times each week. (It is preferable that patients receive ECP treatments on consecutive days within a week, but there should never be > 4 days between the ECP treatments within a week.) Methylprednisolone will be started at 2mg/kg daily dose and may be tapered by reducing dose each week at the following reductions: Daily Dose (mg/kg) 1 1.5 2 1.0 3 0.70 4 0.50 5 0.40 6 0.30 7 0.20 8 0.10

Other Names:

Uvadex+ ECP

Experimental: Uvadex+ECP

Drug: Methoxsalen+ECP, Methylprednisolone

Other Names:

Uvadex+ ECP

Procedure: Ecp

ECP or Extra Corporeal Phototherapy will be used with UVADex

Outcome Measures

Primary Outcome Measures

To compare the safety and efficacy of ECP treatment combined with high dose corticosteroids versus high dose corticosteroids alone, in patients with newly diagnosed acute GvHD (Grades II to III) that developed within 100 days following an allo HPCT. [8 weeks]
The primary efficacy analysis will be performed on the primary endpoint. The primary efficacy variable in this study is complete resolution of acute GvHD, defined as less than Grade I acute GvHD, according to the Glucksberg-Seattle criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent must be obtained prior to conducting any study procedure.
Patients must be greater than or equal to 18 years old and weigh greater than or equal to 40 kg (88 lb).
Patients must have received an allogeneic hematopoietic BMT or PBSCT with myeloablative or reduced-intensity conditioning and have a new onset of acute GvHD, Grades II to III, which includes the skin and developed within 100 days following an allo-HPCT.
Patients must have received an allogeneic hematopoietic BMT or PBSCT from a related or unrelated donor that is matched at a minimum at the HLA-A, -B, and -DR loci (i.e., at least a 6 out of 6 match). HLA-A and -B match should be determined by serologic testing, and HLA-DR should be matched by molecular methods.
Patients must be receiving only a calcineurin inhibitor at study entry as part of their acute GvHD prophylactic regimen. Patients may have received additional immunosuppressants for acute GvHD prophylaxis prior to study entry.
Patients must have a Karnofsky performance greater than or equal to 50.
Patients must be able and willing to comply with all study procedures.
Patients must receive, or must have received, the first corticosteroid dose of approximately 2.0 mg/kg/day but no more than 2.5 mg/kg/day (methylprednisolone equivalent) within 24 hours of the initial diagnosis of Grade II to III acute GvHD. (Up to 2.5 mg/kg/day is allowed for inadvertent dosing fluctuations for reasons other than lack of response.)
Female patients must be one of the following: postmenopausal, surgically incapable of bearing children, practicing an acceptable method of birth control (acceptable methods include hormonal contraceptives, intrauterine device, and spermicide and barrier). Abstinence or partner/spouse sterility may also qualify at the Investigator's discretion. If a female patient is of childbearing potential, she must have a negative urine pregnancy test at screening. Male patients must also commit to using adequate contraceptive precautions (condoms). All patients (both males and females of childbearing potential) must commit to using adequate contraceptive precautions throughout their participation in the study and for at least 3 months following their last ECP treatment.

Exclusion Criteria:

Patients who have been diagnosed with chronic GvHD, including de novo chronic GvHD, prior to 100 days following an allo-HPCT.
Patients who have received donor lymphocyte infusions.
Patients with uncontrolled life-threatening infections.
Patients who have a white blood cell (WBC) count < 1.5 x 10^9/L (1,500/mcL).
Patients who have a platelet count < 20.0 x 10^9/L (20,000/mcL), despite platelet transfusion.
Patients whose total bilirubin is greater than or equal to 22 mg/dL.
Patients who have an International Normalized Ratio (INR) greater than or equal to 2.
Patients who are enrolled in any concomitant investigation for the treatment of acute GvHD.
Patients who are unable to tolerate the extracorporeal volume shifts associated with ECP treatment due to the presence of any of the following conditions: uncompensated congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary disease, severe asthma, renal failure, hepatic encephalopathy, or hepatorenal syndrome.
Female patients whose hemoglobin (Hgb) is < 8.5 g/dL or male patients whose Hgb is < 10.0 g/dL at screening, despite packed red blood cell transfusion.
Patients who have a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.
Patients who have a known hypersensitivity or allergy to Oxsoralen (methoxsalen).
Patients who have a known hypersensitivity or allergy to both heparin and citrate products.
Female patients who are pregnant and/or lactating.
Patients who have co-existing melanoma, basal cell or squamous cell skin carcinoma, aphakia, photosensitive disease (e.g., porphyria, systemic lupus erythematosus, or albinism), white blood cell count > 25,000 cells/mm3, previous splenectomy, or coagulation disorders.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	58109
3	Weill Medical College of Cornell University	New York	New York	United States	10021
4	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
5	Leukemia and Bone Marrow Transplant Center - Avera Cancer Institute	Sioux Falls	South Dakota	United States	57117
6	Royal Brisbane Women's Hospital	Brisbane		Australia	4029
7	Saint Vincent's Hospital	Darlinghurst		Australia	NSW 2010
8	Westmead Hospital	Westmead		Australia	NSW 2145
9	Medical University of Vienna	Vienna		Austria	A-1090
10	Universite Catholique De Louvain	Brussels		Belgium	1200
11	University Hospital Gasthuisberg	Leuven		Belgium	B30000
12	Centre Hopitalier Universitaire Sart Tilman Liege	Liege		Belgium	4000
13	Vancouver General Hopsital	Vancouver	British Columbia	Canada	V5Z 4E3
14	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
15	Maisonneuve-Rosemont Hopital	Montreal		Canada	H1T 2M4
16	Royal Victoria Hospital	Montreal		Canada	H3A 1A1
17	Centre Hospitalier Universitaire Hospital Bordeaux	Bordeaux		France
18	St. Louis Hospital	Paris		France	75010
19	University of Dresden	Dresden		Germany	D-01307
20	Klinikum der Universitat Erlangen-Nurnberg	Erlangen		Germany	91054
21	Universitats Hautklinik	Essen		Germany	45122
22	Universitatskrankenhaus Hamburg-Eppendorf	Hamburg		Germany	20246
23	University of Koln	Koln		Germany	50924
24	Universitatsklinikum Leipzig	Leipzig		Germany	04103
25	Ludwig-Maximillians-Universitat Munchen	Munchen		Germany	81377
26	Universitat Regensburg	Regensburg		Germany	D-93042
27	University of Rostock	Rostock		Germany	18057
28	Stammzelltransplantationzentrum der Universitat Wurzbrug	Wurzburg		Germany	97080
29	San Martino Hospital	Genova		Italy	16132
30	Universita di Siena Policlinico Le Scotte	Sienna		Italy	i-50139
31	Utrecht University Medical Center	Utrecht		Netherlands	3508 G
32	Kantonsspital Basel	Basel		Switzerland	CH 4031
33	Hammersmith Hospital	London		United Kingdom	W12 0NN
34	Royal Victoria Infirmary	Newcastle		United Kingdom	NE1 4LP
35	Rotheram General Hospital	Rotheram Yorkshire		United Kingdom	S60