E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with newly diagnosed acute GVHD grades II to IV |
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MedDRA Classification |
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 |
The primary endpoint is the complete resolution of GVHD manifestations without additional therapy for GVHD before response is evaluated on day 28 (week 4) after study initiation. Patients who require additional therapy for GVHD in the first 4 weeks after study initiation are considered to be treatment failures for the primary endpoint. Patients who die within the first 4 weeks after start of study regardless of GVHD status at the time of death are also regarded as treatment failures.
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E.2.2 | Secondary objectives of the trial |
The following secondary endpoints will be assessed and compared between study arms: Complete response rate by day 56 and day 84 after study initiation Time to complete resolution of acute GVHD to first-line therapy Duration of response to first-line therapy of acute GVHD Cumulative dose ofsteroids in mg/kg/day from day 0 to days 28 and 56 after study initiation Time to discontinuation of steroids as first-line therapy of acute GVHD Percent of patients in need of secondary treatment for acute GVHD Complete response rate to secondary treatment of acute GVHD assessed on day 28 after start of second-line therapy Incidence of bacterial, viral and fungal infections until day 84 and 6 months after study initiation Incidence of recurrence of malignant disease at 6 months and 12 months after study initiation Transplant-related mortality at 6 months and 12 months after study initiation Overall survival at day 6 months and 12 months after study initiation Side effects of ECP
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age > 18 years - Patients who develop after allogeneic cell transplantation new onset acute GVHD, clinical grades II to IV will be eligible. The diagnosis of GVHD will be made on the basis of clinical features, and confirmed histologically according to standard criteria. (27,28) - Treatment for less than 72 hours with 2 mg/kg/day prednisolone prior to randomization and first cycle of ECP. - Absolute neutrophil count greater than 0.5 X 109/L for at least 3 days. Absence of uncontrolled infection. - Karnofsky performance score > 50% - Signed written informed consent - Female patients must be one of the following: postmenopausal, surgically incapable of bearing children, practicing an acceptable method of birth control. If a female patient is of childbearing potential, she must have a negative pregnancy test prior to study entry and in monthly intervals thereafter. - Patients must be able and willing to comply with all study procedures.
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E.4 | Principal exclusion criteria |
- Patients who have received more than one prior allogeneic BMT or PBSCT - Patients who received donor lymphocyte infusions (DLI) - Patients who have a known hypersensitivity or allergy to 8-methoxypsoralen - Patients with uncontrolled infections at onset of acute GVHD. -Patients with serious hemorrhage and/or gastrointestinal bleeding - Patients who had previous treatment with ECP. - Patients who received treatment with prednisolone for > 72 hours. - Patients unable to tolerate removal of > 500 ml of circulating blood volume required for the ECP procedure. - Patients with a platelet count < 20 X 109/L despite platelet transfusions. - Poor likelihood of full cooperation in the study and/or poor compliance anticipated. - Patients with a serious psychiatric disorder. - Patients who are currently participating in another study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the complete resolution of GVHD manifestations without additional therapy for GVHD before response is evaluated on day 28 (week 4) after study initiation. Patients who require additional therapy for GVHD in the first 4 weeks after study initiation are considered to be treatment failures for the primary endpoint. Patients who die within the first 4 weeks after start of study regardless of GVHD status at the time of death are also regarded as treatment failures. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |