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

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

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.

Study Overview

• Status: Completed
• Conditions: ADV Infection Post Allo-HSCT
• Intervention / Treatment: Biological: Cytovir-ADV

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
  • Newcastle, United Kingdom
    • Royal Victoria Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients:

1. Age 16 years or younger
2. Scheduled to undergo an allogeneic HSCT with an unrelated donor, mismatched unrelated donor, mismatched family donor or haplo identical donor
3. 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
4. Negative serology for HIV 1 + 2, HepB, HepC, Syphilis, hCG.

Donors

1. Meets requirements of Directive 2004/23/EC as amended and the UK statutory instruments pursuant therein
2. Negative serology for HIV 1 + 2, HepB, HepC, Syphilis, hCG
3. Passed medical assessment for stem cell donation
4. HdADV seropositive
5. Signed informed consent
6. Age 16 years or older

Exclusion Criteria:

Patients

1. Pregnant or lactating females
2. Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae
3. Human Immunodeficiency Virus (HIV) infection

Donors

1. Pregnant or lactating females
2. (assessed prior to apheresis) Platelets < 50x109/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cytovir-ADV; Adenovirus-specific T-cells

Biological: Cytovir-ADV; 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; Other Names: Adenovirus-specific T-cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Cell Medica Ltd
• Collaborators: Technology Strategy Board, United Kingdom
• Investigators: Principal Investigator: Waseem Qasim, Institute of Child Health, London

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: February 11, 2013
• First Submitted That Met QC Criteria: March 27, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 23, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Adenoviridae Infections
• Other Study ID Numbers: CM-2011-02