E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Newly Diagnosed Acute Graft-versus-Host Disease(GvHD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018651 |
E.1.2 | Term | Graft versus host disease |
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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 |
The primary objective of this study is to compare the safety and efficacy of ECP treatment combined with high dose corticosteroids versus high dose corticosteroids alone, in the treatment of patients with newly diagnosed acute GvHD (Grades II to III) that developed within 100 days following an allo-HPCT. |
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E.2.2 | Secondary objectives of the trial |
overall survival (time elapsed from the date of randomization to the date of death, for any cause), relapse-free survival (time elapsed from the date of randomization to the date of primary disease relapse or the date of death for any cause), time to first occurrence of an acute GvHD flare, incidence and type of serious infections, incidence and severity of chronic GvHD, time to onset of chronic GvHD, change in health performance measures (i.e, Karnofsky score) from baseline, partial response of acute GvHD from baseline according to the Glucksberg-Seattle criteria, change in quality of life (SF-36 and FACT-BMT) measures from baseline. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Signed informed consent must be obtained prior to conducting any study procedure Patients must be >= 18 years old and weigh >= 40 kg (88 lb) Patients must have received an allogeneic hematopoietic BMT or PBSCT with myeloablative or reduced-intensity conditioning and have a new onset of acute GvHD, Grades II to III, which includes the skin and developed within 100 days following an allo-HPCT Patients must have received an allogeneic hematopoietic BMT or PBSCT from a related or unrelated donor that is matched at a minimum at the HLA-A, -B, and -DR loci (i.e., at least a 6 out of 6 match). HLA-A and -B match should be determined by serologic testing, and HLA-DR should be matched by molecular methods Patients must be receiving only a calcineurin inhibitor at study entry as part of their acute GvHD prophylactic regimen. Patients may have received additional immunosuppressants for acute GvHD prophylaxis prior to study entry Patients must have a Karnofsky performance >= 50 Patients must be able and willing to comply with all study procedures. Key inclusion and exclusion criteria (continued) Patients must receive, or must have received, the first corticosteroid dose of approximately 2.0 mg/kg/day but no more than 2.5 mg/kg/day (methylprednisolone equivalent) within 24 hours of the initial diagnosis of Grade II to III acute GvHD. (Up to 2.5 mg/kg/day is allowed for inadvertent dosing fluctuations for reasons other than lack of response.) Female patients must be one of the following: postmenopausal, surgically incapable of bearing children, practicing an acceptable method of birth control (acceptable methods include hormonal contraceptives, intrauterine device, and spermicide and barrier). Abstinence or partner/spouse sterility may also qualify at the Investigator's discretion. Male patients must also commit to using adequate contraceptive precautions (condoms). All patients (both males and females of childbearing potential) must commit to using adequate contraceptive precautions throughout their participation in the study and for at least 3 months following their last ECP treatment. |
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E.4 | Principal exclusion criteria |
Patients who have been diagnosed with chronic GvHD, including de novo chronic GvHD, prior to 100 days following an allo-HPCT Patients who have received donor lymphocyte infusions Patients with uncontrolled life-threatening infections Patients who have a white blood cell (WBC) count < 1.5 x 109/L (1,500/ᄉL) Patients who have a platelet count < 20.0 x 109/L (20,000/ᄉL), despite platelet transfusion Patients whose total bilirubin is >= 22 mg/dL Patients who have an International Normalized Ratio (INR) >= 2 Patients who are enrolled in any concomitant investigation for the treatment of acute GvHD Patients who are unable to tolerate the extracorporeal volume shifts associated with ECP treatment due to the presence of any of the following conditions: uncompensated congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary disease, severe asthma, renal failure, hepatic encephalopathy, or hepatorenal syndrome Patients who have a known hypersensitivity or allergy to psoralen (methoxsalen) Patients who have a known hypersensitivity or allergy to both heparin and citrate products Patients who have co-existing melanoma, basal cell or squamous cell skin carcinoma, aphakia, photosensitive disease (e.g., porphyria, systemic lupus erythematosus, or albinism), white blood cell count > 25,000 cells/mm3, previous splenectomy, or coagulation disorders. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable in this study is complete resolution of acute GvHD, defined as less than Grade I acute GvHD, according to the Glucksberg-Seattle criteria. Treatment success for the purposes of the primary efficacy endpoint is defined as complete resolution of acute GvHD at Weeks 4 and 8, in the absence of any of the following criteria: Patients who receive second-line therapy for GvHD at any time through Week 8. Patients who receive corticosteroids, > 2.5 mg/kg/day methylprednisolone equivalent, at any time through Week 8. |
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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 | No |
E.6.4 | Safety | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | |
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 |