E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CMV reactivation after allogeneic stem cell transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 |
To assess the feasibility, tolerability and safety of administration of donor or patient derived CMV pp65 specific T cells in patients with CMV reactivation or CMV disease after alloSCT. |
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E.2.2 | Secondary objectives of the trial |
- To determine the presence of CMV specific T cells at different time points after infusion of CMV pp65 specific T cells.
- To evaluate whether administration of CMV pp65 specific T cells in patients with persistent CMV reactivation or CMV disease after alloSCT leads to complete or partial responses.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age 0-75 year
- recipient of alloSCT for standard indication according to national- and European Group for blood and Marrow Transplantation-guidelines (see appendix D)
- Possibility to obtain PBMC by leukapheresis from the CMV-seropositive donor or availability of peripheral blood stem cell graft (PBSCT) or of a CD34-negative subfraction of a CD34-positively selected PBSCT product of the donor prepared and cryopreserved at a GMP-facility or stem cell center.
- CMV reactivation treatment failure (persistent CMV DNA load of more than 1000 cp/ml or CMV disease after 2 weeks of adequate treatment with antiviral therapy or relapse of CMV DNA load of more than 1000 cp/ml within 4 weeks after adequate treatment with antiviral therapy or contraindication for treatment with antiviral therapy at the discretion of the physician) or CMV disease (organ dysfunction (pneumonitis, enteritis, retinitis, encephalitis, hepatitis, and bone marrow suppression) due to CMV infection).
- Written informed consent by the patient and/or parent(s) or legal guardian(s). |
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E.4 | Principal exclusion criteria |
- Life expectation < 3 months.
- End stage irreversible multi-system organ failure.
- Pregnant or lactating women.
- Severe psychological disturbances.
- Patient HIV positive.
- Donor HIV positive. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The number of events of acute GvHD, death and all other adverse events.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- After the first 3, 6 and 10 patients an interim analysis will be performed by the principal investigator. And at the end of the study.
- End of the study is defined as 6 months after the infusion of CMV pp65 specific T cells of patient number 15 or at time of subsequent DLI of patient number 15. |
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E.5.2 | Secondary end point(s) |
- The number of CMV specific T cells at different time points after infusion of CMV pp65 specific T cells.
- The number of complete responses or partial responses of CMV reactivation or CMV disease after infusion of CMV pp65 specific T cells. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- After the first 3, 6 and 10 patients an interim analysis will be performed by the principal investigator. And at the end of the study.
- End of the study is defined as 6 months after the infusion of CMV pp65 specific T cells of patient number 15 or at time of subsequent DLI of patient number 15. |
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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 | No |
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | 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 | 3 |
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 | 0 |
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 |