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

NCT ID: NCT00282503

Last Updated: 2017-08-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

methylprednisolone equivalent.

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

Group Type: ACTIVE_COMPARATOR

Methoxsalen+ECP, Methylprednisolone

Intervention Type: 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

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

Group Type: EXPERIMENTAL

Methoxsalen+ECP, Methylprednisolone

Intervention Type: 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

Ecp

Intervention Type: PROCEDURE

ECP or Extra Corporeal Phototherapy will be used with UVADex

Interventions

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

Intervention Type: DRUG

Ecp

ECP or Extra Corporeal Phototherapy will be used with UVADex

Intervention Type: PROCEDURE

Other Intervention Names

Uvadex+ ECP

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Gainesville, Florida, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Weill Medical College of Cornell University

New York, New York, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Leukemia and Bone Marrow Transplant Center - Avera Cancer Institute

Sioux Falls, South Dakota, United States

Royal Brisbane Women's Hospital

Brisbane, , Australia

Saint Vincent's Hospital

Darlinghurst, , Australia

Westmead Hospital

Westmead, , Australia

Medical University of Vienna

Vienna, , Austria

Universite Catholique De Louvain

Brussels, , Belgium

University Hospital Gasthuisberg

Leuven, , Belgium

Centre Hopitalier Universitaire Sart Tilman Liege

Liège, , Belgium

Vancouver General Hopsital

Vancouver, British Columbia, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hopital

Montreal, , Canada

Royal Victoria Hospital

Montreal, , Canada

Centre Hospitalier Universitaire Hospital Bordeaux

Bordeaux, , France

St. Louis Hospital

Paris, , France

University of Koln

Cologne, , Germany

University of Dresden

Dresden, , Germany

Klinikum der Universitat Erlangen-Nurnberg

Erlangen, , Germany

Universitats Hautklinik

Essen, , Germany

Universitatskrankenhaus Hamburg-Eppendorf

Hamburg, , Germany

Universitatsklinikum Leipzig

Leipzig, , Germany

Ludwig-Maximillians-Universitat Munchen

München, , Germany

Universitat Regensburg

Regensburg, , Germany

University of Rostock

Rostock, , Germany

Stammzelltransplantationzentrum der Universitat Wurzbrug

Würzburg, , Germany

Universita di Siena Policlinico Le Scotte

Siena, Sienna, Italy

San Martino Hospital

Genova, , Italy

Utrecht University Medical Center

Utrecht, , Netherlands

Kantonsspital Basel

Basel, , Switzerland

Hammersmith Hospital

London, , United Kingdom

Royal Victoria Infirmary

Newcastle, , United Kingdom

Rotheram General Hospital

Rotheram Yorkshire, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; France; Germany; Italy; Netherlands; Switzerland; United Kingdom

Other Identifiers

Acute GvHD-1

Identifier Type: -

Identifier Source: org_study_id