Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection

Study Overview
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Brief Summary
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To evaluate the safety and efficacy for treatment of persistent CMV infection in hematopoietic cell transplant (HCT) recipients.

Detailed Description
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HCT recipients who are receiving immunosuppressive agents to control graft versus host diseases (GVHD) are at high risk for serious CMV infection due to CMV reactivation or reinfection during their post-transplant period. Antiviral agents used to treat CMV infection have well-known side effects such as bone marrow suppression causing cytopenia and renal toxicities. Therefore, patients in a serious condition would have a higher probability of antiviral treatment-related toxicities and also increased possibility for prolonged antiviral treatment, thus development of antiviral resistance and risk of treatment failure. Allogeneic HCT recipients are typically lack of these CMV-specific T cells during the post-transplant period and their immune function can be further repressed especially when they are on additional immunosuppressive agents to prevent GVHD. Therefore, these patients may benefit from CMV-specific T cell adoptive transfer.

Official Title
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Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection in Allogeneic Hematopoietic Cell Transplant Recipients

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Biological: IFN-γ positive selected T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Less than 66 years old Allogeneic HCT recipients who received stem cells from related CMV positive serology donors AND recipients have persistent CMV infection more than 2 weeks on antiviral treatment Exclusion Criteria: HCT recipients with severe graft versus host disease, grade 3 or more OR organ dysfunction (brain, heart, lung, liver, and kidney): altered mentality, extracorporeal membrane oxygenation, mechanical ventilator, increased liver enzymes 5 times above upper normal values, bilirubin level >3 mg/dL, CrCl < 30 mL/min

Ages Eligible for Study
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Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: allogeneic HSCT<br>The present study will investigate in a single-center (Samsung Medical Center), open-label, single arm by direct infusions of donor-derived CMV-spefic IFN-γ positive T-cells for the treatment of refractory CMV infection in allogeneic hematopoietic stem cell transplant (HSCT) recipients. | Biological: IFN-γ positive selected T-cells<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of enriched IFN-Υ+ T-cells upon pp65 stimulation |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy of CMV infection, defined as reduction of CMV viremia, ex vivo enrichment of CMV antigen (pp65) -specific T cells in peripheral blood. | Treatment efficacy defined as reduction of CMV viremia, ex vivo enrichment of CMV antigen (pp65) -specific T cells in peripheral blood. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell therapy, CMV