Trial registered on ANZCTR


Trial ID
ACTRN12613000981729
Ethics application status
Approved
Date submitted
30/08/2013
Date registered
3/09/2013
Date last updated
29/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
This study is assessing the feasibility of generating expanded T cells for the treatment of cytomegalovirus (CMV) reactivation and disease, and the subsequent evaluation of safety.
Scientific title
Phase I open label clinical trial of autologous T cell therapy for the treatment of cytomegalovirus (CMV) reactivation and disease after transplantation
Secondary ID [1] 283111 0
NIL
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus 289958 0
Condition category
Condition code
Infection 290329 290329 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There will be a single treatment arm. Patients will donate 250 - 300mL of blood, from which T cells will be isolated and expanded. A minimum of 2 and a maximum of 6 intravenous infusions of 1-2 x10e7 /m2 autologous ex vivo expanded, polyclonal, bulk, CMV-specific T cells will be given at weeks 0,2,4,6,10 and 14. The number of infusions may be limited by the number of cells generated.
Intervention code [1] 287830 0
Treatment: Other
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290361 0
Primary Outcome 1: To determine the feasibility of generating ex-vivo expanded polyclonal CMV-specific T cells from SOT (solid organ transplant) recipients.
Assessed by: Medical History, physical examination, vital signs, blood tests.
Timepoint [1] 290361 0
Screening
Primary outcome [2] 290362 0
Primary Outcome 2: To determine the safety of adoptive transfer of up to six doses of CMV-specific T cells into SOT recipients with CMV reactivation or disease.
Assessed by: Reporting of adverse events such as fatigue, fever, high blood pressure, or pain, clinical history, physical examination, vital observations, and laboratory blood studies
Timepoint [2] 290362 0
Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 22, 26, 30, 34, 38, and 42
Secondary outcome [1] 313367 0
nil
Timepoint [1] 313367 0
not applicable

Eligibility
Key inclusion criteria
1) Transplant recipients who were transplanted by, and/or are currently under the care of, a physician at the appropriate clinical facility.
2). CMV infection that falls into one of the following categories:
(2a) CMV reactivation (as defined by PCR) or disease (as defined by histology) following successful initial therapy, or
(2b) Persistent CMV disease (no response to 2 weeks of salvage foscarnet or other second line antiviral agent), or
(2c) Persistent CMV replication (more than 6 weeks by PCR) despite appropriate antiviral therapy, or
(2d) 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) Aged 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) ECOG status greater than 3 (Karnofsky performance score less than 30 : disabled, no self-care. Totally bedridden, or confined to chair)
3) Markers of active HBV, HCV, HIV, HTLV I and II and syphilis infection (presence of HbsAg, HepC antibody, HIV antibody, antibodies to HTLV I and II and positive serological test for syphilis, or positive nucleic acid test (NAT) for HIV, HBV or HCV)
4) Uncontrolled graft rejection.
5) Steroid doses greater than 1mg/kg/day of prednisone, or equivalent
6) Insufficient T cells for in vitro expansion
7) Women who are lactating, pregnant, or unwilling to use adequate contraception

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)
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
Statistical methods / analysis
Safety: The primary measure of safety of CTL adoptive transfer is via adverse events reporting. These will be represented and assessed as follows. 1. Line listings of individuals with clinical and laboratory adverse reactions. 2. Summaries of adverse clinical events including graft versus host disease by severity and relation to adoptive transfer of CMV-CTL 3. Shift tables for laboratory parameters. 4. Graphical representation of selected laboratory values over time. Sample Size: Given 30 participants with 6 exposures per participant the study has a 0.999 probability of observing at least one participant experiencing an adverse event if the probability of that event occurring is assumed to be 0.2 and every exposure produces the AE in those people who are susceptible. Equivalent probabilities for observing AEs which affect 1 in 10 people and 1 in 15 people are 0.958 and 0.874 respectively. Alternatively, using exact (binomial) confidence intervals, if 0 of the 30 participants experienced a particular AE, we would be 95% confident that the population rate for this AE lies somewhere in the range 0% to 11.6%. If 1 of the 30 participants experienced a particular AE, the corresponding 95% confidence interval is 0.08% to 17.2% and for 2 of 30 the 95% confidence interval is 0.08% to 22.1%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 1461 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 1462 0
The Prince Charles Hospital - Chermside
Recruitment hospital [3] 3535 0
The Royal Adelaide Hospital - Adelaide

Funding & Sponsors
Funding source category [1] 287866 0
Charities/Societies/Foundations
Name [1] 287866 0
QIMR Berghofer Flagship Program on Immunotherapy
Address [1] 287866 0
QIMR Berghofer Medical Research Institute
300 Herston Rd, Herston, QLD 4006
Country [1] 287866 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute.
Address
300 Herston Rd, Herston, QLD 4006
Country
Australia
Secondary sponsor category [1] 286595 0
None
Name [1] 286595 0
Address [1] 286595 0
Country [1] 286595 0
Other collaborator category [1] 277595 0
Individual
Name [1] 277595 0
A/Prof. Daniel Chambers
Address [1] 277595 0
The Prince Charles Hospital
Rode Road
Chermside Qld 4032
Country [1] 277595 0
Australia
Other collaborator category [2] 278378 0
Individual
Name [2] 278378 0
Associate Professor Scott Campbell
Address [2] 278378 0
Princess Alexandra Hospital
Ipswich Rd, Woolloongabba, Qld 4103
Country [2] 278378 0
Australia
Other collaborator category [3] 278379 0
Individual
Name [3] 278379 0
Dr Chien-Li Holmes-Liew
Address [3] 278379 0
Royal Adelaide Hospital, North Terrace, Adelaide SA 5000
Country [3] 278379 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289810 0
Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 289810 0
QIMR Berghofer Medical Research Institute.
300 Herston Rd
Herston QLD 4006
Australia
Ethics committee country [1] 289810 0
Australia
Date submitted for ethics approval [1] 289810 0
Approval date [1] 289810 0
23/08/2013
Ethics approval number [1] 289810 0
P1553
Ethics committee name [2] 292475 0
Metro North Hospital and Health Service Human Research Ethics Committee
Ethics committee address [2] 292475 0
The Prince Charles Hospital, Rode Rd, Chermside Qld 4032
Ethics committee country [2] 292475 0
Australia
Date submitted for ethics approval [2] 292475 0
26/07/2013
Approval date [2] 292475 0
09/08/2013
Ethics approval number [2] 292475 0
HREC/13/QPCH/210

Summary
Brief summary
This study involves participants who have undergone solid organ transplantation and are either experiencing human cytomegalovirus (CMV) disease or are at risk of developing it. The study is assessing the feasibility of generating T cells (a type of white blood cell) that target CMV, and the effect of these cells when infused into participants. Eligible participants will donate 250-300mL of blood to expand CMV-specific T cells which will form their treatment. Participants will receive 2-6 intravenous infusions of T cells. The effects of the treatment will be studied by monitoring signs and symptoms and by blood tests. Total length of involvement in the study will be no longer than 10 months.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 42542 0
Prof Rajiv Khanna
Address 42542 0
QIMR Berghofer Medical Research Institute.
300 Herston Rd, Herston QLD 4006
Country 42542 0
Australia
Phone 42542 0
+61 7 3362 0385
Fax 42542 0
+61 7 3845 3510
Email 42542 0
Rajiv.Khanna@qimrberghofer.edu.au
Contact person for public queries
Name 42543 0
Dr Michelle Neller
Address 42543 0
QIMR Berghofer Medical Research Institute.
300 Herston Rd
Herston QLD 4006
Australia
Country 42543 0
Australia
Phone 42543 0
+61-7-3362 0412
Fax 42543 0
+61 7 3845 3510
Email 42543 0
immunotherapy@qimrberghofer.edu.au
Contact person for scientific queries
Name 42544 0
Prof Rajiv Khanna
Address 42544 0
QIMR Berghofer Medical Research Institute.
300 Herston Rd, Herston QLD 4006
Country 42544 0
Australia
Phone 42544 0
+61 7 3362 0385
Fax 42544 0
+61 7 3845 3510
Email 42544 0
Rajiv.Khanna@qimrberghofer.edu.au