Clinical trial NCT00282503: Extracorporeal Photoimmune Therapy With UVADEX for the Treatment of Acute Graft Versus-Host Disease
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Graft-versus-Host Disease
Keywords: aGvHD
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2006-01-26
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent must be obtained prior to conducting any study procedure.
2. Patients must be greater than or equal to 18 years old and weigh greater than or equal to 40 kg (88 lb).
3. 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.
4. 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.
5. 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.
6. Patients must have a Karnofsky performance greater than or equal to 50.
7. Patients must be able and willing to comply with all study procedures.
8. 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.)
9. 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:

1. Patients who have been diagnosed with chronic GvHD, including de novo chronic GvHD, prior to 100 days following an allo-HPCT.
2. Patients who have received donor lymphocyte infusions.
3. Patients with uncontrolled life-threatening infections.
4. Patients who have a white blood cell (WBC) count \< 1.5 x 10\^9/L (1,500/mcL).
5. Patients who have a platelet count \< 20.0 x 10\^9/L (20,000/mcL), despite platelet transfusion.
6. Patients whose total bilirubin is greater than or equal to 22 mg/dL.
7. Patients who have an International Normalized Ratio (INR) greater than or equal to 2.
8. Patients who are enrolled in any concomitant investigation for the treatment of acute GvHD.
9. 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.
10. 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.
11. Patients who have a poor tolerability of venipuncture or a lack of adequate venous access for required treatments and blood sampling.
12. Patients who have a known hypersensitivity or allergy to Oxsoralen (methoxsalen).
13. Patients who have a known hypersensitivity or allergy to both heparin and citrate products.
14. Female patients who are pregnant and/or lactating.
15. 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.

Primary outcomes:
measure: 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.
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Leukemia and Bone Marrow Transplant Center - Avera Cancer Institute
state: South Dakota
city: Brisbane
country: Australia
facility: Royal Brisbane Women's Hospital
city: Darlinghurst
country: Australia
facility: Saint Vincent's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Brussels
country: Belgium
facility: Universite Catholique De Louvain
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hopitalier Universitaire Sart Tilman Liege
city: Vancouver
country: Canada
facility: Vancouver General Hopsital
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hopital
city: Montreal
country: Canada
facility: Royal Victoria Hospital
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire Hospital Bordeaux
city: Paris
country: France
facility: St. Louis Hospital
city: Dresden
country: Germany
facility: University of Dresden
city: Erlangen
country: Germany
facility: Klinikum der Universitat Erlangen-Nurnberg
city: Essen
country: Germany
facility: Universitats Hautklinik
city: Hamburg
country: Germany
facility: Universitatskrankenhaus Hamburg-Eppendorf
city: Koln
country: Germany
facility: University of Koln
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Munchen
country: Germany
facility: Ludwig-Maximillians-Universitat Munchen
city: Regensburg
country: Germany
facility: Universitat Regensburg
city: Rostock
country: Germany
facility: University of Rostock
city: Wurzburg
country: Germany
facility: Stammzelltransplantationzentrum der Universitat Wurzbrug
city: Genova
country: Italy
facility: San Martino Hospital
city: Sienna
country: Italy
facility: Universita di Siena Policlinico Le Scotte
city: Utrecht
country: Netherlands
facility: Utrecht University Medical Center
city: Basel
country: Switzerland
facility: Kantonsspital Basel
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Rotheram Yorkshire
country: United Kingdom
facility: Rotheram General Hospital
Study officials:
References: