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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00282503
Other study ID # Acute GvHD-1
Secondary ID
Status Terminated
Phase Phase 3
First received January 24, 2006
Last updated August 14, 2017
Start date January 2006

Study information

Verified date August 2017
Source Mallinckrodt
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 19
Est. completion date
Est. primary completion date June 2007
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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
Procedure:
Ecp
ECP or Extra Corporeal Phototherapy will be used with UVADex

Locations

Country Name City State
Australia Royal Brisbane Women's Hospital Brisbane
Australia Saint Vincent's Hospital Darlinghurst
Australia Westmead Hospital Westmead
Austria Medical University of Vienna Vienna
Belgium Universite Catholique De Louvain Brussels
Belgium University Hospital Gasthuisberg Leuven
Belgium Centre Hopitalier Universitaire Sart Tilman Liege Liege
Canada Maisonneuve-Rosemont Hopital Montreal
Canada Royal Victoria Hospital Montreal
Canada Princess Margaret Hospital Toronto Ontario
Canada Vancouver General Hopsital Vancouver British Columbia
France Centre Hospitalier Universitaire Hospital Bordeaux Bordeaux
France St. Louis Hospital Paris
Germany University of Dresden Dresden
Germany Klinikum der Universitat Erlangen-Nurnberg Erlangen
Germany Universitats Hautklinik Essen
Germany Universitatskrankenhaus Hamburg-Eppendorf Hamburg
Germany University of Koln Koln
Germany Universitatsklinikum Leipzig Leipzig
Germany Ludwig-Maximillians-Universitat Munchen Munchen
Germany Universitat Regensburg Regensburg
Germany University of Rostock Rostock
Germany Stammzelltransplantationzentrum der Universitat Wurzbrug Wurzburg
Italy San Martino Hospital Genova
Italy Universita di Siena Policlinico Le Scotte Sienna
Netherlands Utrecht University Medical Center Utrecht
Switzerland Kantonsspital Basel Basel
United Kingdom Hammersmith Hospital London
United Kingdom Royal Victoria Infirmary Newcastle
United Kingdom Rotheram General Hospital Rotheram Yorkshire
United States University of Michigan Comprehensive Cancer Center Ann Arbor Michigan
United States University of Florida Gainesville Florida
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

Sponsors (2)

Lead Sponsor Collaborator
Mallinckrodt PRA Health Sciences

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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
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