Randomised adoptive transfer of cytomegalovirus-specific cytotoxic T lymphocytes (CMV CTLs) after stem cell transplant

Phase 2

Completed

• Conditions: Cytomegalovirus (CMV) infection after haemopoietic stem cell transplant; Infections and Infestations; Cytomegaloviral disease

• Registration Number: ISRCTN53325562
• Lead Sponsor: Cell Medica Ltd (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-08-19
• Study Completion: 2012-06-01
• Last Update Posted: 1 April 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 36

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The frequency of CMV reactivation measured by quantitative polymerase chain reaction (PCR) during the first year following transplantation

Secondary Outcome Measures

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