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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Graft-versus-Host Disease
• Intervention / Treatment: Drug: Methoxsalen+ECP, Methylprednisolone; Procedure: Ecp

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4029
    • Royal Brisbane Women's Hospital
  • Darlinghurst, Australia, NSW 2010
    • Saint Vincent's Hospital
  • Westmead, Australia, NSW 2145
    • Westmead Hospital
• Austria
  • Vienna, Austria, A-1090
    • Medical University of Vienna
• Belgium
  • Brussels, Belgium, 1200
    • Université Catholique de Louvain
  • Leuven, Belgium, B30000
    • University Hospital Gasthuisberg
  • Liege, Belgium, 4000
    • Centre Hopitalier Universitaire Sart Tilman Liege
• Canada
  • Montreal, Canada, H1T 2M4
    • Maisonneuve-Rosemont Hopital
  • Montreal, Canada, H3A 1A1
    • Royal Victoria Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E3
      • Vancouver General Hopsital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• France
  • Bordeaux, France
    • Centre Hospitalier Universitaire Hospital Bordeaux
  • Paris, France, 75010
    • St. Louis Hospital
• Germany
  • Dresden, Germany, D-01307
    • University of Dresden
  • Erlangen, Germany, 91054
    • Klinikum der Universitat Erlangen-Nurnberg
  • Essen, Germany, 45122
    • Universitäts Hautklinik
  • Hamburg, Germany, 20246
    • Universitatskrankenhaus Hamburg-Eppendorf
  • Koln, Germany, 50924
    • University of Koln
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
  • Munchen, Germany, 81377
    • Ludwig-Maximillians-Universitat Munchen
  • Regensburg, Germany, D-93042
    • Universitat Regensburg
  • Rostock, Germany, 18057
    • University of Rostock
  • Wurzburg, Germany, 97080
    • Stammzelltransplantationzentrum der Universitat Wurzbrug
• Italy
  • Genova, Italy, 16132
    • San Martino Hospital
  • Sienna, Italy, i-50139
    • Universita di Siena Policlinico Le Scotte
• Netherlands
  • Utrecht, Netherlands, 3508 G
    • Utrecht University Medical Center
• Switzerland
  • Basel, Switzerland, CH 4031
    • Kantonsspital Basel
• United Kingdom
  • London, United Kingdom, W12 0NN
    • Hammersmith Hospital
  • Newcastle, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Rotheram Yorkshire, United Kingdom, S60
    • Rotheram General Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Michigan
    • Ann Arbor, Michigan, United States, 58109
      • University of Michigan Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Leukemia and Bone Marrow Transplant Center - Avera Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Mallinckrodt
• Collaborators: PRA Health Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (Estimate): January 26, 2006

Study Record Updates

• Last Update Posted (Actual): August 16, 2017
• Last Update Submitted That Met QC Criteria: August 14, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: aGvHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Photosensitizing Agents; Dermatologic Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Methoxsalen
• Other Study ID Numbers: Acute GvHD-1