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

NCT00282503 | Terminated Phase 3

• 1 other identifier: Acute GvHD-1
• Study Type: interventional
• Target: 19
• Locations: 10 countries
• Sites: 34

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.

Conditions

Acute Graft-versus-Host Disease

Keywords

aGvHD

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  8 weeks

Study Arms (2)

methylprednisolone equivalent.

ACTIVE COMPARATOR

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

Drug: Methoxsalen+ECP, Methylprednisolone

Uvadex+ECP

EXPERIMENTAL

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; Procedure: Ecp

Interventions

Methoxsalen+ECP, Methylprednisolone DRUG

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

Also known as: Uvadex+ ECP

Uvadex+ECP; methylprednisolone equivalent.

Ecp PROCEDURE

ECP or Extra Corporeal Phototherapy will be used with UVADex

Uvadex+ECP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mallinckrodt: lead
• PRA Health Sciences: collaborator

Study Sites (35)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 58109, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Leukemia and Bone Marrow Transplant Center - Avera Cancer Institute

Sioux Falls, South Dakota, 57117, United States

Location

Royal Brisbane Women's Hospital

Brisbane, 4029, Australia

Location

Saint Vincent's Hospital

Darlinghurst, NSW 2010, Australia

Location

Westmead Hospital

Westmead, NSW 2145, Australia

Location

Medical University of Vienna

Vienna, A-1090, Austria

Location

Universite Catholique De Louvain

Brussels, 1200, Belgium

Location

University Hospital Gasthuisberg

Leuven, B30000, Belgium

Location

Centre Hopitalier Universitaire Sart Tilman Liege

Liège, 4000, Belgium

Location

Vancouver General Hopsital

Vancouver, British Columbia, V5Z 4E3, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve-Rosemont Hopital

Montreal, H1T 2M4, Canada

Location

Royal Victoria Hospital

Montreal, H3A 1A1, Canada

Location

Centre Hospitalier Universitaire Hospital Bordeaux

Bordeaux, France

Location

St. Louis Hospital

Paris, 75010, France

Location

University of Koln

Cologne, 50924, Germany

Location

University of Dresden

Dresden, D-01307, Germany

Location

Klinikum der Universitat Erlangen-Nurnberg

Erlangen, 91054, Germany

Location

Universitats Hautklinik

Essen, 45122, Germany

Location

Universitatskrankenhaus Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

Ludwig-Maximillians-Universitat Munchen

München, 81377, Germany

Location

Universitat Regensburg

Regensburg, D-93042, Germany

Location

University of Rostock

Rostock, 18057, Germany

Location

Stammzelltransplantationzentrum der Universitat Wurzbrug

Würzburg, 97080, Germany

Location

Universita di Siena Policlinico Le Scotte

Siena, Sienna, i-50139, Italy

Location

San Martino Hospital

Genova, 16132, Italy

Location

Utrecht University Medical Center

Utrecht, 3508 G, Netherlands

Location

Kantonsspital Basel

Basel, CH 4031, Switzerland

Location

Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, NE1 4LP, United Kingdom

Location

Rotheram General Hospital

Rotheram Yorkshire, S60, United Kingdom

Location

MeSH Terms

Interventions

Methylprednisolone; Eosinophil Cationic Protein

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Endoribonucleases; Ribonucleases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Eosinophil Granule Proteins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2006
• First Posted: January 26, 2006
• Study Start: January 1, 2006
• Primary Completion: June 1, 2007
• Last Updated: August 16, 2017

Record last verified: 2017-08

Locations

AU (3); CA (4); US (5); BE (3); FR (2); DE (10); IT (2); CH (1); NL (1); GB (3)