E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Graft Versus Host Disease |
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E.1.1.1 | Medical condition in easily understood language |
Graft Versus Host Disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066260 |
E.1.2 | Term | Acute graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068908 |
E.1.2 | Term | AGVHD |
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 |
Proportion of patients in each treatment arm who experience a CRGVHD or PRGVHD at day 57 after randomization, without treatment failure (initiation of secondary treatment) |
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E.2.2 | Secondary objectives of the trial |
-Proportion of patients in each treatment arm who experience a CRGVHD or PRGVHD at other indicated daysuntil 2 years after initiation of study-treatment, without treatment failure (initiation of secondary treatment)
-Time to CRGVHD or PRGVHD
-Amount of immune suppression at other indicated days until 2 years
-Adverse events
-The (immunological) phenotype before and after application of MSC/placebo of responders and non-responders in both groups at different sites
-The immunological genotype of responders and non-responders as well as donors in both groups
-Quality of life
-Cost-effectiveness
-Relapse of the underlying disease (e.g. hematological malignancy)
-Progression-free survival
-Incidence and severity of chronic GVHD
-Overall survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Any age;
-Previously treated with allo-SCT/ DLI;
-Grade II-IV acute GVHD involving gut and/or liver, confirmed by histology of involved tissues, however, the first infusion of MSC can be given without final histological confirmation;
-WHO performance 0-3 ;
-Negative pregnancy test (if applicable);
-Patients must be willing and capable to use adequate contraception during therapy (if applicable);
-Written Informed Consent by the patient and/or parent(s) or legal guardian(s);
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E.4 | Principal exclusion criteria |
-Patients with active, uncontrolled infection;
-Rapid progressive hematological malignancy;
-Patients pre-treated with prednisolone > 1 mg/kg for GVHD, for more than 72 hours prior to randomization/application of MSC;
-Known uncontrolled toxicity for DMSO;
-Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
-Any psychological, familial, sociological and/or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients in each treatment arm who experience a CR-GVHD or PR-GVHD at day 57 after randomization, without treatment failure (initiation of secondary treatment; progression/relapse, or death) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Final analysis will take place when the relevant data (until day 57) of all patients are available and validated |
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E.5.2 | Secondary end point(s) |
-Proportion of patients in each treatment arm who experience a CR-GVHD or PR- GVHD at indicated days after initiation of study-treatment, without treatment failure (initiation of secondary treatment, progression/relapse, or death)
-Time to CR-GVHD or PR-GVHD
-Amount of immune suppression at indicated days (and cumulative exposure of steroid till above mentioned time points)
- Adverse events
- The (immunological) phenotype before and after application of MSC of responders and non-responders in both groups at different sites including the validation of a defined predictive early phenotype
-The immunological genotype of responders and non-responders as well as donors in both groups
- Quality of life at indicated days
- Cost-effectiveness as determined by hospital admission days from randomization until day 57 calculated against the price of MSC
- Relapse of the underlying disease (e.g. hematological malignancy)
- Incidence and severity of chronic GVHD
- Progression-free survival, defined as time from randomization until progression or relapse (of the underlying disease), or death whichever the cause
- Overall survival, defined as time from randomization until deach whichever the cause. Patients still alive at the date of last contact, will be censored |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Final analysis will take place when the relevant data (until 2 years) of all patients are available and validated |
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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 | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 14 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 14 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |