E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
New onset high risk acute GvHD following allogeneic SCT |
Neu auftretende akute GvHD mit hohem Risiko nach allogener SCT
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E.1.1.1 | Medical condition in easily understood language |
New onset high risk acute Graft-versus-Host-Disease following allogeneic (of nonself origin) Stem Cell Transplantation |
Neu auftretende akute Spender-gegen-Empfänger-Erkrankung mit hohem Risiko nach Transplantation von Stammzellen, die nicht vom Patienten selbst stammen
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018653 |
E.1.2 | Term | Graft-versus-host disease <GVHD> |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To improve day 28 GvHD complete response rate for high risk (Ann Arbor Score 2/3) GvHD patients from the historical rate of 37% to 52% by treatment with ECP and high dose systemic corticosteroids (2 mg/kg).
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Verbesserung der GvHD-Gesamtansprechrate am Tag 28 bei Hochrisiko-GvHD-Patienten (Ann Arbor Score 2/3) von bisher 37% auf 52% durch Behandlung mit ECP und hochdosierten systemischen Kortikosteroiden (2 mg / kg).
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E.2.2 | Secondary objectives of the trial |
To decrease 6-month NRM from the historical rate of 30% to 20% in patients treated on this clinical trial. |
Verringerung der 6-Monats-NRM von der historischen Rate von 30% auf 20% bei Patienten, die in dieser klinischen Studie behandelt werden. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (Glucksberg grade I-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 7 days of methylprednisolone ≤2 mg/kg/day (or IV Methyprednisolone equivalent) during the period from the initiation of systemic steroid treatment for acute GvHD until study therapy begins. 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 unless due to aGvHD 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 before screening. 9. ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days before screening 10. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol (see section 11). 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 start ECP within 5 working days of initiation of systemic steroid treatment for acute GvHD are not permitted to par-ticipate.
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E.4 | Principal 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 leu-koencephalopathy (PML) 5. Pregnant or nursing (lactating) women 6. Use of other drugs for the treatment of acute GvHD apart from on-going 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 carci-noma 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/ul 18.Coagulopathy 19. Known photosensitive disease like systemic lupus erythematosus, porphyrias or albinism
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this clinical study is the proportion of complete response (that is, the per-cent of patients with skin, liver, and GI GvHD all stage 0) at day 28 of study treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At day 28 of study treatment |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: 1. Overall survival at 1 year 2. Cumulative incidence of NRM at 6 months and at 1 year 3. Overall response rate (CR + PR) at day 28 and 56. PR is defined as improvement in one or more organs involved with GvHD symptoms without progression in others. For a response to be scored as PR on day 28 or 56, the patient must be in PR on day 28 or 56 and have had no intervening non-study therapy for acute GvHD. 4. Cumulative incidence of treatment-refractory GvHD (defined as ab-sence of CR or PR on day 28 of treatment or who receive additional immunosuppression prior to day 28) 5. Cumulative incidence of severe GI GvHD stage 3 or 4 6. Time to discontinuation of steroid therapy 7. Number of lines of GvHD therapy (defined as the initiation of a new acute GvHD therapy, regard-less of duration) 8. Cumulative incidence of chronic GvHD 9. Number of serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- on days 28 and/or 56 - Overall survival after 1 year - Cumulative incidence of NRM at 6 months and at 1 year
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last follow-up visit of the last patient |
letzter Kontrollbesuch des letzten Patienten |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |