Cytomegalovirus Pneumonia, Cytomegalovirus Viremia, T-Lymphocyte Immunodeficiency
Conditions
Keywords
donor-derived T lymphocytes
Brief summary
Treatment of CMV in a patient with profound combined immunodeficiency, who has viremia and pneumonia, using CMV-specific donor-derived T lymphocytes (CMV-VST).
Detailed description
Treatment of CMV in a patient with profound combined immunodeficiency, who has viremia and pneumonia, using CMV-specific donor-derived T lymphocytes (CMV-VST), a cell therapy product containing a mixture of donor lymphocytes, reactive to peptides derived from cytomegalovirus. After having receipt of therapy, the patient will have clinical assessments twice a week until discharge from the inpatient unit. After discharge, assessments will be performed on a weekly basis for three months. From 3-12 months, the patient will be seen monthly and then every three months till 2 years post planned hematopoietic stem cell transplantation. After 2 years, survival status will be assessed every 6 months through year 15.
Interventions
BIOLOGICALCMV-VST
30-40 x 10\^3 viable CD3+ cells/kg
Sponsors
Alberta Precision Laboratories
Alberta Health services
University of Alberta
University of Calgary
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
0 Years to 20 Years
Healthy volunteers
No
Inclusion criteria
* profound combined immunodeficiency * cytomegalovirus (CMV) infection * viremia * pneumonia
Exclusion criteria
* Receiving a steroid dose of ≥ 0.5 mg/kg of prednisolone equivalent * Receiving antithymocyte globulin or similar anti-T-cell antibody therapy, methotrexate, or other antimetabolite-type immunosuppressants that are toxic to proliferating T cells, and extracorporeal * Receiving checkpoint inhibitor agents (eg, nivolumab, pembrolizumab, ipilimumab) are within 3 drug half-lives of the most recent dose to cycle 1 day 1. * Administration of another investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of study | Enrollment to 24 months | Evaluate the feasibility of conducting this study, evaluated in terms of whether or not the study could be completed as laid out in the protocol in the time allotted. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Weekly to 3 months | AEs assessed according to CTCAE grading criteria. |
| Efficacy of Intervention | Weekly to 3 months | Change in viremia from baseline according to PCR testing after the intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | Enrollment to 24 months | Death of participant |
| CMV-reactive T cell number | Weekly to 3 months | The number of CMV-reactive T cells in the patient's blood will be enumerated using an CMV-ELISpot assay. |
| Total CMV-reactive T cell activity | Weekly to 3 months | The total amount of INF γ secreted from all CMV-reactive T cells in the patient's blood to measured using a commercially available ELISA kit (QuantiFERON-CMV). This will allow track the cumulative response to CMV by the reactive T cells over time. |
| Engraftment failure | Enrollment to 24 months | Assessment of evidence of engraftment failure from clinical evaluations |
| RNA sequencing | Weekly to 3 months | RNA sequencing, to characterize CMV-reactive T cell biology and track individual VST clones |
| Serum cytokine analysis | Weekly to 3 months | Serum cytokines, to estimate total CMV-reactive T cell activity and host response to treatment |
| CMV-reactive T cell phenotyping | Weekly to 3 months | Flow cytometry will be used to characterize CMV-reactive T cell phenotype |
| Graft versus host disease | Enrollment to 24 months | Assessment of evidence of graft versus host disease (GVHD) from clinical evaluations |
| Transplant associated thrombotic microangiopathy | Enrollment to 24 months | Assessment of evidence of Transplant associated thrombotic microangiopathy (TA-TMA) from clinical evaluations |
Countries
Canada
Outcome results
None listed