Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease
Condition: Steroid Refractory Acute Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Methoxsalen; Extracorporeal Photopheresis (ECP)
Intervention description: Sterile solution used in conjunction with photopheresis procedure.
Intervention MeSH terms: Methoxsalen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No

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 (ECP) in
      pediatric participants with steroid-refractory aGvHD. The study is composed of Screening,
      Treatment, and Follow-up Periods.
    

Eligibility criteria:

        Inclusion:

          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 participants with lower gastrointestinal (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 participants with disease confined to upper
                  GI disease or lesser degrees of skin GvHD

               -  Participants 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 × 10^9/liter (L)

               -  Creatinine level < 2 times the upper limit of normal

          5. For participants with isolated upper GI symptoms, pre-Screening biopsy results to
             confirm diagnosis of aGvHD

          6. Female participants 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 participants 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:

          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 × 10^9/L, despite platelet transfusion

          7. Inability to tolerate the extracorporeal volume shifts associated with ECP treatment

          8. Uncontrolled GI bleeding

          9. Veno-occlusive liver disease

         10. Life expectancy < 4 weeks

         11. Participant requires invasive ventilation or vasopressor support

         12. Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of
             seronegativity within 6 months of screening is required)

         13. Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients

         14. Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose
             Formula-A (ACD-A)

         15. Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus,
             albinism) or aphakia

         16. Coagulation disorders that cannot be corrected with simple transfusion

         17. Co-existing melanoma, basal cell, or squamous cell skin carcinoma

         18. Previous splenectomy

         19. White blood cell count greater than 25,000 cubic millimeter (mm^3)

         20. Currently being treated with any systemic immunosuppressive or biologic therapy for
             the treatment of a medical condition other than aGvHD

         21. Female participant is breastfeeding or pregnant

         22. Any medical concerns that may pose risk to the participant

         23. Any psychological, familial, sociological, and/or geographical condition that may
             potentially hamper compliance with the study protocol and follow-up schedule