chronic CMV infection after allogeneic hematopoietic stem cell transplantation in children, refractory to conventional antiviral treatment
Conditions
Interventions
Product Name: Streptacells - CMV specific donor lymphocytes enriched by imunomagnetic separation
Pharmaceutical Form: Injection
INN or Proposed INN: Virus-specific CD8+ T-cells
Other descriptive name:
Sponsors
Univerzita Karlova v Praze, 2. lékarská fakulta
Eligibility
Sex/Gender
All
Inclusion criteria
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 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
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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);Secondary Objective: 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;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;Timepoint(s) of evaluation of this end point: at least six months from the time of adoptive transfer in the last enroled patients | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: at least six months from the time of adoptive transfer in the last enroled patient | — |
Countries
Czech Republic
Contacts
Public ContactBoard of the Dean
Charles University in Prague, 2nd Faculty of Medicine
Outcome results
None listed