E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic CMV infection after allogeneic hematopoietic stem cell transplantation in children, refractory to conventional antiviral treatment |
|
E.1.1.1 | Medical condition in easily understood language |
chronic CMV infection after allogeneic hematopoietic stem cell transplantation in children, refractory to conventional antiviral treatment |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Toxicity
safety and toxicity of the adoptive transfer of Streptamer selected CMV-specific T-cells from third party donor (other than original donor used for hematopoietic stem cell transplantation) |
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E.2.2 | Secondary objectives of the trial |
Efficacy of adoptive transfer - reduction of viral load
CMV-specific immune reconstitution after AT - presence of IFNg+/IL2+ CD8+ T-cells by FACS analysis after AT
Finding recommendation dose for future phase II clinical trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for patients - patients after allogeneic HSCT with progression of CMV viral load in peripheral blood (by RQ PCR) for 2 consecutive weeks despite the proper treatment with virostatics or patients unable to tolerate conventional GCV or FCV treatment due to severe toxicity - reagents for HLA type of patient available - absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial - written informed consent from patient/patients’ guardian and donor must be given prior patient registration to the trial according to ICH/GCP
Inclusion criteria for donors - healthy CMV-seropositive third party haploidentical family donor - CMV serological positivity proven by serology - Male donors will be preferred due to lower risk of GVHD induction (due to pregnancy in female donors which increase alloreactivity of CD8+ T cells) - Written informed consent from the donor must be given prior patient registration to the trial according to ICH/GCP |
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E.4 | Principal exclusion criteria |
Exclusion criteria for patients - missing written informed consent from patient or donor - medication with >1 mg/kg/day of Prednisolon - acute GVHD grade III-IV
Exclusion criteria for donors - missing written informed consent from patient or donor - CMV negative donors - diseases which may be harmful to donor or patient (as defined in the guidance for the eligibility of stem cell donors, e.g. HIV, Hepatitis B, Hepatitis C) |
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E.5 End points |
E.5.1 | Primary end point(s) |
- safety of the procedure as sessed by graft versus host disease (GVHD) grade III-IV or secondary graft rejection rate - safety of procedure also include infusion related complications such as rash, fever, hypertension or hypoxia |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at least six months from the time of adoptive transfer in the last enroled patients |
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E.5.2 | Secondary end point(s) |
Efficacy of procedure -Only limited data about efficacy will be available because of small cohort of patients enrolled to this phase I trial -Efficacy end-point will be a result of translational research study where polychromatic flow cytometry and RQ PCR will address the question about reconstitution of CMV-specific CD8+ T-cells and reduction of a viral load |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at least six months from the time of adoptive transfer in the last enroled patient |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | Yes |
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) | 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 | Yes |
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 | 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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The trial will be closed six months from the time of adoptive transfer in the last enroled patient.
Stopping criteria Evidence of an unacceptable rate of GVHD grade III-IV, secondary graft failure or non-hematological toxicity grade 3 or higher following the infusion of CMV-specific CD8+ T cells will constitute trial stopping criteria (TSC). |
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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 |