Randomised adoptive transfer of cytomegalovirus-specific cytotoxic T lymphocytes (CMV CTLs) after stem cell transplant
| ISRCTN | ISRCTN53325562 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN53325562 |
| ClinicalTrials.gov number | NCT01220895 |
| Secondary identifying numbers | RG_07-186 |
- Submission date
- 11/07/2008
- Registration date
- 19/08/2008
- Last edited
- 13/03/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Mrs Karen Hodgkin
Scientific
Scientific
Cell Medica Ltd
27 Fitzroy Square
London
W1T 6ES
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request patient information material |
| 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 |
| Study acronym | CMV-ASPECT (Alternate donor Study of Pre-Emptive Cellular Therapy) |
| Study objectives | 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. |
| Ethics approval(s) | West Midlands Research Ethics Committee, 21/04/2008, ref: 08/H1208/17 |
| Health condition(s) or problem(s) studied | 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. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | The frequency of CMV reactivation measured by quantitative polymerase chain reaction (PCR) during the first year following transplantation |
| Secondary outcome measures | 1. CMV-specific immune reconstitution by detection of circulating T-cell responses to CMV in the first year following transplant 2. 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 study start date | 01/10/2010 |
| Completion date | 01/06/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 36 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/10/2010 |
| Date of final enrolment | 01/06/2012 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cell Medica Ltd
London
W1T 6ES
United Kingdom
W1T 6ES
United Kingdom
Sponsor information
Cell Medica Ltd (UK)
Industry
Industry
27 Fitzroy Square
London
W1T 6ES
United Kingdom
| Website | http://www.cellmedica.co.uk |
|---|---|
"ROR" |
https://ror.org/027q99w81 |
Funders
Funder type
Charity
Leukaemia Research Fund (UK) - new grant award (ref: 05071)
No information available
Cell Medica Ltd
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
13/03/2019: No publications found, verifying study status with principal investigator.
05/03/2019: Internal review.
22/05/2017: No publications found, verifying study status with principal investigator.
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 overall trial start date was changed from 01/09/2008 to 01/10/2010.
5. The overall trial end date was changed from 31/08/2011 to 01/06/2012.
6. 'Cell Medica Ltd' was added to the sources of funding field.
7. The sponsor information for this trial was updated. The previous sponsor was University of Birmingham (UK). The new sponsor details can be found in the relevant field. Secondary collaborators include: Leukaemia Lymphoma Research; National Health Service, Blood and Transplant; University of Birmingham.
