Acute graft-versus-host disease (aGvHD) MedDRA version: 20.1 Level: PT Classification code 10018651 Term: Graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: UVADEX™ 20 Mikrogramm/ml Lösung zur Modifikation einer Blutfraktion
Pharmaceutical Form: Solution for blood fraction modification
INN or Proposed INN: metho
Sponsors
Therakos, Inc.
Eligibility
Sex/Gender
All
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 of 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 =65 years) no F.1.3.1 Number of subjects for this age range
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 or 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 the follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of extracorporeal photopheresis (ECP) in pediatric patients with steroid-refractory aGvHD; Secondary Objective: • 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 ;Primary end point(s): The proportion of patients reaching an overall response (CR+PR) after 4 weeks (Day 28) of ECP treatment, regardless of steroid tapering, or fewer treatments if they discontinued treatment.;Timepoint(s) of evaluation of this end point: after 4 weeks (Day 28) of ECP treatment, regardless of steroid tapering. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): * Safety parameters including vital signs, laboratory tests, and spontaneously reported AEs and SAEs * Proportion of patients who achieve an overall response 8 weeks (Day 56) and 12 weeks (Day 84) after initiation of ECP treatment * Duration of response, defined as the length of time a patient maintains a response through Week 16 of the Follow-up Period on a perpatient basis * Proportion of patients who achieve an overall response after 4 weeks (Day 28, 8 weeks (Day 56) and 12 weeks (Day 84) of ECP treatment according to the modified Glucksberg criteria (see Appendix B: Modified Glucksberg Criteria) Source data will be collected for each patient and entered into the eCRF, and a scoring algorithm will be applied to calculate the grade of aGvHD using the Modified Glucksberg Criteria * Cumulative dose of daily steroids administered from diagnosis of aGvHD to 12 weeks (Day 84) after initiation of ECP treatment * Organ-specific grade at 4 weeks (Day 28, 8 weeks (Day 56) and 12 weeks (Day 84) after initiation of ECP treatment ;Timepoint(s) of evaluation of this end point: see above | — |
Countries
Austria, France, Germany, Hungary, Italy, Poland, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactProject Management
Therakos, Inc.
Outcome results
None listed