Extracorporal Photopheresis With UVADEX Plus Standard Steroid Treatment for High Risk Acute Graft-versus-host Disease

• Status: Recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single arm phase 2 trial which includes patients with high risk acute GVHD defined as Ann Arbor score 2 or 3. The purpose of the study is to improve the outcome of these patients in terms of response to treatment and treatment related mortality. All patients will receive the study intervention (ECP with Uvadex). The study hypothesis is that the treatment plan will produce a day 28 complete response rate higher than or equal to 52%, which will represent an improvement of 15% compared with the standard of care (37%). The rate of complete response to standard of care treatment is based on observed data in similar patients treated within the Mount Sanai Acute GVHD International Consorium (MAGIC). Patients will be treated for 56 days and followed for one year to also enable evaluation of long term outcome.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: Clinical Trial Center North (CTC North GmbH & Co. KG); Mallinckrodt; University Medical Center Regensburg
• Treatments: Methoxsalen

Criteria

Inclusion Criteria:

1. New onset high risk acute GvHD (Ann Arbor score 2/3 as defined in Appendix A) following allogeneic SCT. Any clinical severity in accordance with Glucksberg grade II-IV is eligible.

2. Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.

3. No prior systemic treatment for acute GvHD except for a Maximum of 3 days of prednisone ≤2 mg/kg/day (or IV methylprednisolone equivalent). Topical skin steroid treatment and non-absorbable oral steroid treatment for GI GvHD are permissible.

4. Age 18 years or older.

5. Platelet count > 25.000 (including platelet support)

6. Eastern Coorperative Oncology Group (ECOG) score of 0≤2

7. Negative pregnancy test within 10 days before start of study if the patient is a woman of child-bearing Age

8. Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGvHD within 3 days of enrollment.

9. ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days of enrollment.

10. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.

11. Written informed consent from patient.

12. Biopsy of acute GvHD target organ is strongly recommended but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 5 days of Initiation of systemic steroid treatment for acute GvHD are not permitted to participate

Exclusion Criteria:

1. Progressive or relapsed malignancy

2. Uncontrolled active infection

3. Patients with chronic GvHD

4. History of or current diagnosis of progressive multifocal leukoencephalopathy (PML)

5. Pregnant or nursing (lactating) women

6. Use of other drugs for the treatment of acute GvHD apart from ongoing GvHD prophylaxis and corticosteroids

7. Patients on dialysis

8. Patients requiring ventilator support

9. Evidence of known infection with human immunodeficiency virus (HIV) or active hepatitis B

10. Investigational agent within 30 days of enrollment without approval from the Sponsor/ Investigator (PI). (Off-label use of medication is not considered investigational unless in context of a formal study)

11. History of allergic reaction to 8-MOP

12. Concomitant diagnosis of malignant melanoma or basal cell carcinoma

13. Hypersensitivity or allergy to both heparin and citrate products (if hypersensitive or allergic only to one, exclusion does not apply)

14. Inability to tolerate extracorporeal volume shifts associated with ECP

15. Presence of aphakia

16. History of splenectomy

17. Leucocyte count > 25.000/μl

18. Coagulopathy

19. Known photosensitive disease like systemic lupus erythematosus, porphyrias or albinism