Condition category
Infections and Infestations
Date applied
09/03/2012
Date assigned
12/04/2012
Last edited
07/08/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Adenovirus (ADV) infections account for 10% of acute respiratory infections in children but are unlikely to cause serious complications in healthy patients. Following bone marrow transplant, ADV infection occurs in about 30% of paediatric patients and may be responsible for as many as 10% of post-transplant paediatric deaths. Antiviral drugs have some success, but no drug available is indicated for this patient group; current treatment options do not restore immune function. Additionally, currently available antiviral drugs have side effects that may increase the levels of morbidity (illness) in these patients. This study will look at the safety of adenovirus-specific T-cells (ADV-specific immune cells) given to high-risk paediatric patients after bone marrow transplant to treat reactivation of adenovirus.

Who can participate?
Patients considered at highest risk of infection: paediatric patients (aged 16 or younger) with unrelated donors, mismatched family donors or haploidentical (half-matched) donors.

What does the study involve?
Following transplant, patients are routinely monitored for ADV viraemia (presence of ADV virus) and following two consecutive positive results, the selected cell dose will be infused. If a patient is still exhibiting uncontrolled ADV viraemia four weeks following the cell infusion, they will be infused with a higher cell dose. Throughout the study the patients will be asked to give blood samples to assess their immune function and will be closely monitored for side effects through routine medical assessments. Evidence of the treatment’s effectiveness, demonstrated by clearance of ADV virus, will also be recorded.

What are the possible benefits and risks of participating?
The benefits are, if the treatment works, the ADV infection will be better controlled and immunity will be restored, preventing further infection. The main concern for participating is an increase in the incidence of graft-versus-host-disease, in which the white blood cells of the transplanted bone marrow react against the patient’s own body organs and tissues. There are both acute and chronic forms of this complication and it may cause skin rash, diarrhoea and liver inflammation. Because of the methods used, it is unlikely that this increase will be seen; the process will specifically increase the numbers of adenovirus-specific cells only and the number of white blood cells given to the patient is very small, which reduces the risks overall. Additional risks associated with infusion are fever, allergic reactions, infection, inflammation and inefficacy.

Where is the study run from?
The study runs over three hospitals in the UK – Great Ormond Street Hospital, London; Royal Victoria Infirmary, Newcastle and Royal Children’s Hospital, Manchester.

When is the study starting and how long is it expected to run for?
From December 2012 to July 2016.

Who is funding the study?
Cell Medica Ltd and the Technology Strategy Board (UK).

Who is the main contact?
Dr Shreenal Patel
aspire@cellmedica.co.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Waseem Qasim

ORCID ID

Contact details

Institute of Child Health
Great Ormond Street Hospital
30 Guilford Street
London
WC1N 1EH
United Kingdom

Additional identifiers

EudraCT number

2011-001788-36

ClinicalTrials.gov number

NCT01822093

Protocol/serial number

2011-001788-36

Study information

Scientific title

A phase I/II study to investigate the safety of adenovirus-specific T-cells given to high-risk paediatric patients post allogeneic haematopoietic stem cell transplant (HSCT) to prevent or treat reactivation of adenovirus

Acronym

ASPIRE

Study hypothesis

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.

On 28/04/2015 the following changes were made to the trial record:
1. The overall trial start date was changed from 01/07/2012 to 01/12/2012.
2. The overall trial end date was changed from 31/12/2014 to 01/07/2016.

Ethics approval

1. Initial EC approval (NRES Committee London – Riverside) dated 23/08/2012
2. Substantial Amendment 001 approved on 04/10/2012
3. Substantial Amendment 002 approved on 21/06/2013
4. Substantial Amendment 003 approved on 14/04/2014
5. Substantial Amendment 004 approved on 18/09/2014

Study design

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

Primary study design

Interventional

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Allogeneic hematopoietic stem cell transplantation (HSCT) patients considered at high risk of developing adenovirus (ADV) infection

Intervention

Current interventions as of 28/04/2015:
Adenovirus-specific T-cells (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 1x10e5 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

Previous interventions:
Adenovirus-specific T-cells (Cytovir-ADV)

A single dose 5x10e4 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

Intervention type

Other

Phase

Drug names

Primary outcome measures

Current primary outcome measures as of 28/04/2015:
1. Number of subjects with new onset GvHD; Time Frame: 180 days
2. Number of subjects developing NCI Grade 3-4 adverse events; Time Frame: 180 days

Previous primary outcome measures:
1. Toxicity
2. Incidence and severity of GVHD
3. Cytopenias
4. Grade 3-4 adverse events.

Secondary outcome measures

1. Number of reported serious adverse events (SAEs) (Suspected, Unexpected Serious Adverse Reactions [SUSARs] and Suspected, Expected Serious Adverse Reactions [SESARs])
2. Number of detectable HAdV-specific T-cells in vivo at each time point
3. Requirement for second infusion of ADV specific T cells
4. Number of treatment days with antiviral drugs.
5. Number of treatment days with other anti-infective drugs
6. Number of in-hospital days during study period

Overall trial start date

01/12/2012

Overall trial end date

31/07/2016

Reason abandoned

Eligibility

Participant 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 (for manufacturing only):
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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

12-15

Participant 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

Recruitment start date

01/12/2012

Recruitment end date

30/06/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute of Child Health
London
WC1N 1EH
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Royal Manchester Children’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Sponsor information

Organisation

Cell Medica Ltd (UK)

Sponsor details

1 Canal Side Studios
8-14 St Pancras Way
London
NW1 0QG
United Kingdom

Sponsor type

Industry

Website

http://www.cellmedica.co.uk/

Funders

Funder type

Industry

Funder name

Cell Medica Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Technology Strategy Board (UK)

Alternative name(s)

TSB

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

We anticipate publication of a manuscript about 1 year following completion of the CSR

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes