E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MSCs may be useful for treating established severe GVHD after stem cell transplantation. Preliminary data on 40 patients with steroid refractory grade III-IV acute GvHD were recently presented (K Leblanc; European Blood and Marrow Transplantation group, Lyon, march 2007). Among the forty patients treated, nineteen had complete responses, nine showed improvement and seven patients did not respond. There was no apparent correlation between the response and the dose of MSCs given. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate safety, toxicity and feasibility of MSC infusion using a platelet lysate expansion method, for the treatment of acute steroid refractory Graft versus Host disease |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of MSC for the treatment of GVHD, Incidence of infections, Morbidity and mortality of patients treated with MSC, Disease relapse, Immune function and chimerism
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. For screening and MSC culture: newly diagnosed acute grade II-IV GVHD or chronic GVHD with an acute pattern matching grade II-IV after allogeneic stem cell transplantation 2. For infusion: steroid refractory grade II-IV acute GVHD or chronic GVHD with an acute pattern matching grade II-IV after allogeneic stem cell transplantation. 3. Patients must have received 2 mg/kg/day of prednisolon for at least 3 consecutive days and experience progression of GVHD or no response to at least 7 days of steroid treatment. 4. In addition to steroids the patient has received either cyclosporin (trough level 150-250 ng/ml) or tacrolimus (trough level 5-15 ng/ml). Patients with steroid refractory GvHD may be treated with second line therapy according to the clinical practice at the center while waiting for MSC infusion. At each center all patients included in the study should be treated in the same way. 5. Written informed consent.
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E.4 | Principal exclusion criteria |
1. Patients with poor performance, not expected to survive 3 weeks. 2. Donor Chimerism below 90% 3. Active uncontrolled CMV, EBV or fungal infection
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Response of acute GVHD Response is defined as complete or partial resolution of acute GvHD. Assessment of GVHD response as per protocol 1. Complete resolution of GVHD: Control of all signs and symptoms attributed to acute GVHD (consistent with overall grade 0) for at least one month, with or without continued medication with steroids and cyclosporine 2. Partial resolution of GVHD: Control of some signs and symptoms attributed to acute GVHD with an improvement of overall grade by at least two grades for less than one month. 3. Refractory GVHD: No change in signs or symptoms of GVHD within 8 days of MSC infusion 4. Worsening GVHD: Any progress of GVHD signs and symptoms that increase overall grade by one or more grades 8 days after MSC infusion.
1. and 2. will be defined as response. 3. and 4. will be defined as no response.
Evaluation of secondary outcome variables 1. Determination of incidence of chronic GVHD. 2. Survival. 3. Infections. 4. Recurrent disease.
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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 | Yes |
E.7.1.3.1 | Other trial type description |
test safety of platelet lysate expansion method for MSC |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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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Treatment related mortality exceeding 30% within 24h of MSC infusion. Any occurrence of secindary malignancies. Lack of efficacy in the first 5 (adult or pediatric) patients. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |