CMV-specific Donor-derived T Lymphocytes for the Treatment of Recalcitrant CMV Infection in a Patient With Primary Immunodeficiency

Not Applicable

Active, not recruiting

• Conditions: Cytomegalovirus Pneumonia; T-Lymphocyte Immunodeficiency; Cytomegalovirus Viremia
• Interventions: Biological: CMV-VST

• Registration Number: NCT07015801
• Lead Sponsor: University of Calgary

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.

Study Timeline

• Study Start: 2025-04-15
• Status Verified: 2025-05
• Study First Submitted: 2025-05-22
• Study First Submitted QC: 2025-06-06
• Last Update Submitted: 2025-06-06
• Study First Posted: 2025-06-11
• Last Update Posted: 2025-06-11
• Primary Completion: 2027-04
• Study Completion: 2040-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CMV-specific donor-derived T lymphocytes (CMV-VST).	CMV-VST	Mixture of donor lymphocytes, reactive to peptides derived from cytomegalovirus.

Primary Outcome Measures

Name	Time	Method
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	Every 3 months from 12-24 months	Change in viremia from baseline according to PCR testing after the intervention

Secondary Outcome Measures

Name	Time	Method
CMV-reactive T cell number	Every 3 months from 12-24 months	The number of CMV-reactive T cells in the patient's blood will be enumerated using an CMV-ELISpot assay.
Engraftment failure	Enrollment to 24 months	Assessment of evidence of engraftment failure from clinical evaluations
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
Death	Enrollment to 24 months	Death of participant
CMV-reactive T cell phenotyping	Every 3 months from 12-24 months	Flow cytometry will be used to characterize CMV-reactive T cell phenotype
RNA sequencing	Every 3 months from 12-24 months	RNA sequencing, to characterize CMV-reactive T cell biology and track individual VST clones
Serum cytokine analysis	Every 3 months from 12-24 months	Serum cytokines, to estimate total CMV-reactive T cell activity and host response to treatment
Total CMV-reactive T cell activity	Every 3 months from 12-24 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.

Trial Locations

Locations (1)

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada