TKS-2014-001 UVADEX

Principal Investigator: Andrew Harris
Keywords: Uvadex , aGvHD , Steroid , Acute , Graft Department: Pediatric Hematology/Oncology
IRB Number: 00096208 Co Investigator:  
Specialty: Pediatric Hematology and Oncology
Sub Specialties: Blood and Marrow Transplantation
Recruitment Status: Recruiting

Contact Information

Kayla Woodring
kayla.woodring@hsc.utah.edu
(801) 213-3908

Brief Summary

This is a single-arm, open-label, multicenter study of the efficacy of UVADEX (methoxsalen) Sterile Solution in conjunction with THERAKOS CELLEX Photopheresis Systems in pediatric patients with steroid-refractory aGvHD. The study is composed of Screening, Treatment, and Follow-up
Periods.
 
Primary objective:
  • To evaluate the efficacy of extracorporeal photopheresis (ECP) in pediatric patients with steroid-refractory aGvHD.
Secondary objectives:
  • To assess the safety of ECP.
  • To assess the duration of response to ECP.
  • To assess the steroid-sparing effect of ECP.
  • To assess the organ-specific response to ECP.

Inclusion Criteria

INCLUSION CRITERIA
 
Patients must meet all of the following criteria:
 
1. Male or female 1 to 21 years of age at the time of consent
 
2. Steroid-refractory grade B-D aGvHD.
  • Steroid-refractory is defined as a failure to respond to steroid treatment, with failure to respond defined as any grade B-D (IBMTR grading) aGvHD that shows progression ≥ 3 days, or no improvement by 5 days of treatment with 2 mg/kg/day methylprednisolone or equivalent in patients with lower GI or liver disease, or skin disease associated with bullae. Grade D organ involvement will be limited to skin and liver.
  • Steroid refractory may also be defined as a failure to respond to 1 mg/kg/day of methylprednisolone or equivalent in patients with disease confined to upper GI disease or lesser degrees of skin GvHD.
  • Patients with lack of complete response after 2 weeks of steroid treatment.
3. A Lansky scale Performance Status score ≥ 30.
 
4. Laboratory values are within the following limits, assessed within 3 days of the first study treatment:
  • Absolute neutrophil count > 0.5 × 109/L.
  • Creatinine level < 2 times the upper limit of normal.
5. For patients with isolated upper GI symptoms, pre-Screening biopsy results to confirm diagnosis of aGvHD.
 
6. Female patients of childbearing potential and nonsterilized males who are sexually active with a female partner must be practicing highly effective, reliable, and medically approved contraceptive regimen throughout their participation in the study and for 3 months following the last ECP treatment. Or, for the US only, abstinence may be used in place of an approved contraceptive regimen. Females of childbearing potential are those who have reached the onset of menarche, or 8 years of age, whichever comes first. Approved contraceptive methods for female patients of childbearing potential or nonsterilized males who are sexually active with a female partner are as follows:
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  • Established use of oral, injectable, or implanted hormonal methods of contraception.
  • Placement of an intrauterine device or intrauterine system.
7. Signed informed consent/assent is obtained before conducting any study procedures; the parent, legal guardian, or legally authorized representative of a minor must also provide written informed consent.

Exclusion Criteria

EXCLUSION CRITERIA
 
Any of the following would exclude the patient from participation in the study:
 
1. Currently enrolled in another clinical trial for the treatment of aGvHD. 
 
2. Use of any experimental regimens or medication(s) for aGvHD treatment. 
 
3. Treatment with > 2.0 mg/kg/day of methylprednisolone equivalents for aGvHD within 30 days prior to the first study treatment.
 
4. Overt signs of relapse of the underlying condition.
 
5. Uncontrolled viral, fungal, or bacterial infection.
 
6. Platelet count < 20.0 × 109/L, despite platelet transfusion.
 
7. Total bilirubin value ≥ 15 mg/dL.
 
8. Inability to tolerate the extracorporeal volume shifts associated with ECP treatment.
 
9. Uncontrolled GI bleeding.
 
10. Veno-occlusive liver disease.
 
11. Life expectancy < 4 weeks.
 
12. Patient requires invasive ventilation or vasopressor support.
 
13. Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of seronegativity within 6 months of screening is required).
 
14. Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients.
 
15. Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose Formula- A (ACD-A).
 
16. Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism) or aphakia.
 
17. Coagulation disorders that cannot be corrected with simple transfusion.
 
18. Co-existing melanoma, basal cell, or squamous cell skin carcinoma.
 
19. Previous splenectomy.
 
20. White blood cell count greater than 25,000 mm3.
 
21. Currently being treated with any systemic immunosuppressive or biologic therapy for the treatment of a medical condition other than aGvHD.
 
22. Female patient is breastfeeding or pregnant.
 
23. Any medical concerns that may pose risk to the patient.
 
24. Any psychological, familial, sociological, and/or geographical condition that may potentially hamper compliance with the study protocol and follow-up schedule.