Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease

• Status: Terminated
• Trial end date: 2019-07-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mallinckrodt; Therakos, Inc., a Mallinckrodt Company
• Treatments: Methoxsalen; Pharmaceutical Solutions

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