Transfer of CMV specific T-cells for immunotherapy of CMV infection in pediatric patients after hematopoietic stem cell transplantatio
- Conditions
- chronic CMV infection after allogeneic hematopoietic stem cell transplantation in children, refractory to conventional antiviral treatmentTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2012-001335-31-CZ
- Lead Sponsor
- niverzita Karlova v Praze, 2. lékarská fakulta
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 14
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
Are the trial subjects under 18? yes
Number of subjects for this age range: 14
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Toxicity<br><br>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);Secondary Objective: Efficacy of adoptive transfer<br>- reduction of viral load<br><br>CMV-specific immune reconstitution after AT<br>- presence of IFNg+/IL2+ CD8+ T-cells by FACS analysis after AT<br><br>Finding recommendation dose for future phase II clinical trial;Primary end point(s): - safety of the procedure as sessed by graft versus host disease (GVHD) grade III-IV or secondary graft rejection rate<br>- safety of procedure also include infusion related complications such as rash, fever, hypertension or hypoxia;Timepoint(s) of evaluation of this end point: at least six months from the time of adoptive transfer in the last enroled patients
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Efficacy of procedure<br>-Only limited data about efficacy will be available because of small cohort of patients enrolled to this phase I trial<br>-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+<br>T-cells and reduction of a viral load;Timepoint(s) of evaluation of this end point: at least six months from the time of adoptive transfer in the last enroled patient