Condition category
Infections and Infestations
Date applied
11/07/2008
Date assigned
19/08/2008
Last edited
02/10/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Karen Hodgkin

ORCID ID

Contact details

Cell Medica Ltd
27 Fitzroy Square
London
W1T 6ES
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01220895

Protocol/serial number

RG_07-186

Study information

Scientific title

A prospective randomised, phase II study to investigate the efficacy and safety of pre-emptive cytomegalovirus (CMV) adoptive cellular therapy in patients receiving allogeneic haematopoietic stem cell transplant from an unrelated donor. CMV~ASPECT (Alternate donor Study of Pre-Emptive Cellular Therapy)

Acronym

CMV-ASPECT

Study hypothesis

Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality following allogeneic stem cell transplant (SCT). We hypothesise that prophylactic adoptive transfer of human leukocyte antigen (HLA)-multimer selected cytomegalovirus-specific cytotoxic T lymphocytes (CMV-CTLs) after SCT will reduce CMV-related morbidity and mortality through lower frequencies of CMV reactivation during the first year following SCT.

On 22/02/2011 the following changes were made to the trial record:
1. The scientific title was updated. The previous scientific title was: 'A randomised controlled phase II trial of the adoptive transfer of selected cytomegalovirus-specific cytotoxic T lymphocytes (CMV-CTL) after allogeneic stem cell transplantation (SCT) in patients at risk of CMV disease'.
2. The acronym was changed from 'ACE' to 'CMV-ASPECT'.
3.The target number of participants was changed from 78 to 36.
4. The anticipated start date was changed from 01/09/2008 to 01/10/2010.
5. The anticipated end date was changed from 31/08/2011 to 01/06/2012.
6. 'Cell Medica Ltd' was added to the sources of funding field.

Ethics approval

West Midlands Research Ethics Committee, 21/04/2008, ref: 08/H1208/17

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details to request patient information material

Condition

Cytomegalovirus (CMV) infection after haemopoietic stem cell transplant

Intervention

Current interventions as of 22/02/2011:
This trial aims to recruit 36 patients with unrelated donors. Patients will be randomised into one of two arms: pre-emptive infusion with CMV-specific T cells selected by the streptamer selection technique plus standard CMV antiviral therapy versus standard CMV antiviral therapy alone. Patients randomised to receive therapy will be given a single infusion upon CMV reactivation in conjunction with standard best available antiviral drug therapy following SCT.

Previous interventions:
This trial aims to recruit 18 patients with sibling donors and 21 patients with unrelated donors on each treatment arm (78 patients estimated in total). Patients will be randomised into one of two arms - standard practice (control) versus prophylactic infusion of CMV CTLs. Patients randomised to receive therapy will be given a single infusion on day 21 (+/-3 days if infusion falls on a weekend or bank holiday) following SCT. This will consist of up to 10^6/kg donor CMV-specific CD8+ T cells. Patients randomised to the control group will not receive an infusion of CMV-CTL.

On 22/02/2011 the sponsor information for this trial was updated. The new sponsor details can be found in the relevant field below.

Secondary collaborators include: Leukaemia Lymphoma Research; National Health Service, Blood and Transplant; University of Birmingham

The previous sponsor details were:
University of Birmingham (UK)
Edgbaston
Birmingham
B15 2TT
United Kingdom

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

To determine the frequency of CMV reactivation during the first year following transplantation measured by quantitative polymerase chain reaction (PCR)

Secondary outcome measures

1. To monitor CMV-specific immune reconstitution within the first year following transplantation by detection of circulating T-cell responses to CMV in the first year following transplant
2. To determine clinical outcomes (total duration of follow-up: 12 months):
2.1. Time to CMV reactivation
2.2. Use of antiviral therapy
2.3. Incidence of secondary CMV reactivation and CMV disease
2.4. Incidence of acute and chronic graft-versus-host-disease (GvHD)

Overall trial start date

01/10/2010

Overall trial end date

01/06/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 22/02/2011:
1. Age 16 years or older
2. CMV-seropositive allogeneic T cell depleted (alemtuzumab-containing conditioning regimen) HSCT recipient with CMV-seropositive unrelated donor
3. Patient informed consent
4. Prepared to undergo additional study procedures as per study schedule
5. Patient has undergone counselling about risk
6. Donor engraftment (neutrophils > 0.5x10^9/l) (to be assessed prior to CMV-specific T-cell infusion)
7. Single positive CMV PCR result (and to be assessed prior to CMV-specific T-cell infusion)
8. The donor will be selected from the Anthony Nolan Trust registry or other donor registries that have approved the protocol and consent procedure.
9. Donor must have met requirements of EU Tissue and Cells Directive (2004/23/EC) as amended and the UK statutory instruments pursuant therein.
10. Healthy, CMV-seropositive donor - having passed medical for stem cell donation
11. Subject and donor must have negative serology for HIV, hepatitis B and C, syphilis
12. HLA type A*0101, A*0201, A*2402, B*0702, B*0801, B*3501
13. Donor informed consent for stem cell mobilisation leucapheresis and storage

Previous inclusion criteria:
1. Both males and females, aged 16 years or over
2. Patients considered fit for allogeneic peripheral blood stem cell transplant
3. Sibling or matched unrelated allogeneic peripheral blood stem cell transplant (PBSCT) using alemtuzemab
4. CMV-seropositive patient and donor
5. Patients and donor sharing at least one of the following HLA alleles:- HLA-A*0101, HLA*0201, HLA-A*1101, HLA-A*2402, HLA-B*0702, HLA-B*0801, HLA-B*3502
6. Patient willing and able to give consent and comply with trial protocol

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

36

Participant exclusion criteria

Current exclusion criteria as of 22/02/2011:
1. Pregnant or lactating women
2. Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae
3. HIV infection
4. Active acute GVHD > Grade I (to be assessed prior to CMV-specific T-cell infusion)
5. Concurrent use of systemic corticosteroids (to be assessed prior to CMV-specific T-cell infusion)
6. Organ dysfunction (to be assessed prior to CMV-specific T-cell infusion ) as measured by:
6.1. Creatinine > 200 uM/l
6.2. Bilirubin > 50 uM/l
6.3. Alanine transferase > 3x upper limit of normal
7. Donor pregnant or lactating
8. Donor platelets < 50x10^9/l

Previous exclusion criteria:
1. Donors whose stem cells have already been collected and cryopreserved prior to transplant
2. Patients whose donor stem cell harvests are <4.0 x 10^6 CD34 cells/kg will not proceed with the study
3. Bone marrow transplants

Recruitment start date

01/10/2010

Recruitment end date

01/06/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cell Medica Ltd
London
W1T 6ES
United Kingdom

Sponsor information

Organisation

Cell Medica Ltd (UK)

Sponsor details

27 Fitzroy Square
London
W1T 6ES
United Kingdom

Sponsor type

Industry

Website

http://www.cellmedica.co.uk

Funders

Funder type

Charity

Funder name

Leukaemia Research Fund (UK) - new grant award (ref: 05071)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Cell Medica Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes