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Trial registered on ANZCTR


Registration number
ACTRN12609000531213
Ethics application status
Approved
Date submitted
22/06/2009
Date registered
2/07/2009
Date last updated
15/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
T-cell Therapy for CMV (Cytomegalovirus) Disease
Scientific title
Adoptive immunotherapy for the treatment of cytomegalovirus (CMV) reactivation and disease after transplantation.
Secondary ID [1] 574 0
Queensland Institute of Medical Research project number P1211
Universal Trial Number (UTN)
Trial acronym
QR2009-CMV1a
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CMV disease 4654 0
Condition category
Condition code
Infection 4957 4957 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Allogeneic or autologous ex vivo expanded human CMV-specific T cells will be administered by intravenous infusion. Up to six doses will be given at weeks 0, 2, 4, 6, 10, and 14.
Intervention code [1] 4419 0
Treatment: Other
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 5805 0
Feasibility of generating HCMV-specific T cells from HCMV-seropositive allogeneic HSCT donors, or if unavailable, Hematopoietic stem cell transplantation (HSCT) recipients.
Timepoint [1] 5805 0
The investigational product for each study participant will be assessed post production. Interim assessment will be made when 10 study participants have received at least 2 treatments. Overall assessment will be made after treatment of all participants has finished. Stringent quality control tests (sterility media inoculation, cell viability testing, cell counting, staining for phenotypic analysis) will also be performed and a Certificate of Manufacture will be issued when products are released from the facility. The phenotype (CD3, CD4, CD8, CD56 and CD16) of the T cell lines will be analysed by FACS analysis. The degree of HCMV specificity in the final T cell product will be determined by peptide-specific interferon-gamma secretion in a 6-hour intracellular cytokine secretion assay.
Primary outcome [2] 5806 0
Safety of adoptive transfer of up to six doses of HCMV-specific cytotoxic T cells in allogeneic HSCT recipients.
Timepoint [2] 5806 0
Safety will be assessed by adverse event monitoring. Patients will be questioned and toxicities recorded according to the common terminology for adverse events up to one hour post eacht treatment (fortnightly for 4 treatments then each 4 weeks for a further 2 treatments), and each 4 weeks until one year after the first treatment. Interim assessment will be made when 10 study participants have received at least 2 treatments. Overall assessment will be made after treatment of all participants has finished. Physical examination and vital observations will be performed at each clinic visit. Concurrent medications, including immunosuppression and antiviral treatment, will be documented at each visit. GVHD will be scored on a standardised scale (appendix II). Full blood count (FBC) and liver function tests (ELFT) will be performed on a regular basis and HCMV viral load will be determined by quantitative PCR. In patients with target organ disease, repeat tissue biopsy is encouraged where feasible, particularly when HCMV is not detected in peripheral blood at time of enrolment. Adverse events will be recorded at each scheduled visit.
Secondary outcome [1] 241808 0
To evaluate the immunological effect of CMV-specific T cell transfer. This would include measurement of CMV-specific T cell numbers and function by tetramer analysis, ELISPOT, and CMV-Quantiferon.
Timepoint [1] 241808 0
At the time of each treatment (fortnightly for 4 treatments then each 4 weeks for a further 2 treatments), and each 4 weeks until one year after the first treatment.
Secondary outcome [2] 241809 0
To evaluate the clinical effect of CMV-specific T cell transfer. This would include clinical assessment, measurement of CMV viral load, and where applicable, tissue biopsy.
Timepoint [2] 241809 0
At the time of each treatment (fortnightly for 4 treatments then each 4 weeks for a further 2 treatments), and each 4 weeks until one year after the first treatment.

Eligibility
Key inclusion criteria
1) HSCT/SOT recipients who were transplanted by, and/or are currently under the care of, a haematologist or physician at the appropriate clinical facility.
2). CMV infection that falls into one of the following categories:
(a) Recurrent CMV reactivation (as defined by PCR) or disease (as defined by histology) following successful initial therapy, or
(b) Persistent CMV disease (no response to 2 weeks of salvage foscarnet or other second line antiviral agent), or
(c) Persistent CMV replication (more than 6 weeks by PCR) despite appropriate antiviral therapy, or
(d) Any CMV reactivation or disease where anti-viral therapy is contraindicated on the basis of intolerance or end organ limitation (e.g. renal impairment, marrow dysfunction).
3) Absence of uncontrolled intercurrent infection
4) Patient able to provide informed consent
5) Age 18 to 75
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 Uncontrolled intercurrent infection
2 Eastern Cooperative Oncology Group (ECOG)status > 3 (Karnofsky performance score < 30: disabled, no self-care. Totally bedridden, or confined to chair)
3 Markers of active Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) infection (presence of Hepatitis B surface Antigen (HBsAg), Hepatitis C (HepC) antibody, or HIV antibodies)
4 Uncontrolled Graft versus Host disease (GVHD)
5 Steroid doses > 1mg/kg of prednisone, or equivalent

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable (non randomised trial)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3457 0
Other
Name [1] 3457 0
Research Infrastructure Support Services (R.I.S.S)
Address [1] 3457 0
GPO Box 5103 Melbourne, Victoria 3001
Country [1] 3457 0
Australia
Funding source category [2] 285314 0
Government body
Name [2] 285314 0
National Health and Medical Research Council
Address [2] 285314 0
GPO Box 1421 Canberra, Australian Capital Teritory 2601
Country [2] 285314 0
Australia
Primary sponsor type
Other
Name
Queensland Institute of Medical Research
Address
300 Herston Rd
Herston
Queensland 4006
Country
Australia
Secondary sponsor category [1] 3105 0
None
Name [1] 3105 0
Address [1] 3105 0
Country [1] 3105 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5490 0
Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 5490 0
The Queensland Institute of Medical Research,
Post Office Royal Brisbane,QLD, 4029
Ethics committee country [1] 5490 0
Australia
Date submitted for ethics approval [1] 5490 0
22/04/2009
Approval date [1] 5490 0
04/04/2012
Ethics approval number [1] 5490 0
HREC/09/QRBW/197
Ethics committee name [2] 6910 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [2] 6910 0
Research Ethics
Royal Brisbane and Women's Hospital
Level 7, block 7,
Butterfield Street
QLD 4029
Ethics committee country [2] 6910 0
Australia
Date submitted for ethics approval [2] 6910 0
23/06/2009
Approval date [2] 6910 0
Ethics approval number [2] 6910 0

Summary
Brief summary
Since the inception of human organ transplantation, HCMV remains single most-important cause of infectious morbidity and mortality in immunocompromised transplant patients. This project is designed to develop immunotherapeutic strategies based on adoptive transfer of virus- specific killer T cells for the treatment of HCMV infection in transplant patients.

Who is it for?
You can join this study if you have had an allogeneic haematopoietic stem cell transplant or a renal transplant at the Royal Brisbane Hospital and have a CMV infection.

Trial details
Blood will be collected from your stem cell donor (for SCT patients) or yourself and the CMV killer T cells grown in the laboratory (this takes about 3 weeks.) The cells are then tested for sterility and specificity. Once the cells pass these checks they will be infused into yourself: 4 doses at 2 weekly intervals and then a further 2 doses at 4 weekly intervals provided sufficient cells are produced.

The effects of the treatment will be studied by monitoring your signs and symptoms and by blood tests. This will be done at the time of each treatment and then monthly for up to a year from the first treatment. Your total length of involvement will be no longer than 18 months.
Trial website
Trial related presentations / publications
Smith, C. and KHANNA, R. Immune regulation of human herpesviruses and its implications for human transplantation.
Am. J. Transplantation (2013) 13:9-23.

Tey, S.K, Davenport, M., Hill, G. Kennedy, G., Durrant, S., KHANNA, R. and Cromer, D. Post-transplant cytomegalovirus-specific T cell immune reconstitution in the absence of global T cell immunity is associated with a high risk of subsequent virus reactivation" by Bone Marrow Transplant (2014) In press

Tey, S.K., Kennedy, G.A., Cromer, D., Davenport, M.P., Walker, S., Jones, L.I., Crough, T., Durrant, S.T., Morton, J.A., Butler, J.P., Misra, A.K., Hill, G.R. and KHANNA, R. Clinical assessment of anti-viral CD8+ T cell immune monitoring to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications. PLoS ONE (2013) 8: e74744.

KHANNA, R. and Smith. C. Cellular immune therapy for viral infections in transplant patients. Indian J Med Res (2013) 138: 796-807.
Public notes

Contacts
Principal investigator
Name 28649 0
Prof Rajiv Khanna
Address 28649 0
Queensland Institute of Medical Research, 300 Herston Road, Herston 4006 Brisbane
Country 28649 0
Australia
Phone 28649 0
+61 7 3362 0385
Fax 28649 0
+61 7 3845 3510
Email 28649 0
Rajiv.Khanna@qimr.edu.au
Contact person for public queries
Name 11806 0
Dr Katherine Matthews
Address 11806 0
Queensland Institute of Medical Research, 300 Herston Road, Herston 4006 Brisbane
Country 11806 0
Australia
Phone 11806 0
+61 7 3362 0412
Fax 11806 0
+61 7 3845 3510
Email 11806 0
Katherine.Matthews@qimr.edu.au
Contact person for scientific queries
Name 2734 0
Prof Rajiv Khanna
Address 2734 0
Queensland Institute of Medical Research, 300 Herston Road, Herston 4006 Brisbane
Country 2734 0
Australia
Phone 2734 0
61-7- 3362 0385
Fax 2734 0
+ 61 7 3845 3510
Email 2734 0
rajiv.khanna@qimr.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary