Safety Study of ADV-specific T-cells in Paediatric Patients Post Allo-HSCT

Study Overview
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Brief Summary
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Human Adenovirus-specific T-cells can persist and augment impaired adenovirus immune response post allogeneic haematopoietic stem cell transplant, and reduce the requirement for antiviral therapy without toxicity or increasing the occurrence of Graft Versus Host Disease. This is a Phase I/IIa open-label safety study, assessing the effects of administering adenovirus-specific T-cells (Cytovir ADV) to paediatric patients post haematopoietic stem cell transplant.

Official Title
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Phase I/II Study Investigating the Safety of ADV Specific T Cells in High-risk Paediatric Patients Post Allo-HSCT to Treat ADV Reactivation

Conditions
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ADV Infection Post Allo-HSCT

Intervention / Treatment
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* Biological: Cytovir-ADV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: Age 16 years or younger Scheduled to undergo an allogeneic HSCT with an unrelated donor, mismatched unrelated donor, mismatched family donor or haplo identical donor The subject (or legally acceptable representative) must give informed consent (and assent for subjects ≥ 12 years). All subjects will have a parent or guardian provide informed consent and the subject will provide witnessed verbal assent Negative serology for HIV 1 + 2, HepB, HepC, Syphilis, hCG. Donors Meets requirements of Directive 2004/23/EC as amended and the UK statutory instruments pursuant therein Negative serology for HIV 1 + 2, HepB, HepC, Syphilis, hCG Passed medical assessment for stem cell donation HdADV seropositive Signed informed consent Age 16 years or older Exclusion Criteria: Patients Pregnant or lactating females Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae Human Immunodeficiency Virus (HIV) infection Donors Pregnant or lactating females (assessed prior to apheresis) Platelets < 50x109/L

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Cytovir-ADV<br>Adenovirus-specific T-cells | Biological: Cytovir-ADV<br>* A single dose 1x10e4 CD3+ T cells/kg patient weight of Cytovir ADV is prescribed to patients on exhibiting two consecutive PCR positive Adenovirus viraemia results > 1000 copies/ml. Patients are followed up by continued monitoring of Adenovirus viraemia results. If patients exhibit uncontrolled ADV viraemia at ≥ 4 weeks following the first cell dose, they will be prescribed a second cell dose of 10e5 CD3+ T cell/kg. Patients will be monitored for 6 months following infusion of Cytovir ADV. This is a feasibility/pilot study and has no control group<br>* Other names: Adenovirus-specific T-cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with new onset GVHD |  | 180 days | 
| number of subjects developing NCI Grade 3-4 adverse events |  | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of reported Serious Adverse Events (SAEs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Suspected Expected Serious Adverse Reactions (SESARs) |  | 180 days | 
| Number of detectable HAdV-specific T-cells in vivo at each time point |  | 180 days | 
| Requirement for second infusion of HAdV-specific T-cells |  | 180 days | 
| Number of treatment days with antiviral drugs |  | 180 days | 
| Number of treatment days with other anti-infective drugs |  | 180 days | 
| Number of in-hospital days during 6 month post-infusion period |  | 180 days |