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Trial registered on ANZCTR


Registration number
ACTRN12615000656538
Ethics application status
Approved
Date submitted
4/06/2015
Date registered
25/06/2015
Date last updated
14/10/2021
Date data sharing statement initially provided
14/10/2021
Date results provided
14/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I trial of autologous cytomegalovirus (CMV)-specific T cells as adjuvant therapy for primary glioblastoma multiforme
Scientific title
Phase I trial to assess the safety and tolerability of autologous CMV-specific T cells as adjuvant therapy for primary glioblastoma multiforme
Secondary ID [1] 286607 0
QGBM02.1
Universal Trial Number (UTN)
nil
Trial acronym
Immunotherapy for primary glioblastoma
Linked study record

Health condition
Health condition(s) or problem(s) studied:
glioblastoma multiformae 294917 0
Condition category
Condition code
Cancer 295166 295166 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants who meet the trial eligibility criteria following screening and review of blood test results will donate a 250-300 mL blood sample.

The investigational product is autologous CMV-specific T cells, stimulated with autologous peripheral blood mononuclear cells (PBMC) coated with synthetic CMV epitopes. Approximately 200-400mL will be collected from eligible participants in order to generate the investigational product.

GBM patients will be given up to six infusions every 2 - 4 weeks of 1-2 × 10^7/m^2 autologous CMV-specific T cells. The timing of adoptive transfers will be at the discretion of the clinical investigator, based on the patient’s chemotherapy schedule, and the number of cells infused is based on the height and weight of the patient and the number of cells grown.

The cells will be thawed into 20 mL saline, and will be administered to patients intravenously. The T cells will be administered to the patient over 5–15 min by Prof Walker or an appropriately trained delegate. This will allow the slow administration of T cells into the blood.

Participants will be followed up to 1 year from the final cell infusion.
Intervention code [1] 291735 0
Treatment: Other
Comparator / control treatment
nil (single arm phase I study, no comparator group)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294946 0
To assess the tolerability of adoptive transfer of autologous CMV-specific T cells into patients with primary GBM as an adjuvant to standard chemotherapy/radiotherapy. This outcome is assessed using the Functional Assessment of Cancer Therapy Brain Quality of Life Questionnaire.
Timepoint [1] 294946 0
At each treatment (approximately every 4 weeks for up to 6 treatments) and at 1, 2, 3, 4, 6 and 12 months post treatment.
Primary outcome [2] 294948 0
To determine the safety of the adoptive transfer of autologous CMV-specific T cells into patients with primary GBM as an adjuvant to standard chemotherapy/radiotherapy. This outcome is assessed using adverse events as well as full blood count, electrolyte and liver function tests.
Timepoint [2] 294948 0
Adverse event monitoring, clinical examinations and vital sign monitoring are conducted at each infusion.This outcome is assessed at each treatment (approximately every 4 weeks for up to 6 treatments) and at 1, 2, 3, 4, 6 and 12 months after the last treatment.
Primary outcome [3] 294949 0
To determine if autologous CMV-specific T cells can be generated to clinical scale from the blood of patients with primary glioblastoma multiformae. This will be determined by calculating the proportion of patients for whom the minimum number of 2 doses of T cells can be generated (ie two vials of 2 x 10^7 cells/m^2).
Timepoint [3] 294949 0
For each patient, the feasibility of generating the T cell therapy will be known approximately 5 weeks after the collection of 250-300 ml blood for therapy generation. The overall feasibility of generating the CMV-specific T cells for the patient cohort will be calculated at the end of the study.
Secondary outcome [1] 314454 0
nil
Timepoint [1] 314454 0
not applicable

Eligibility
Key inclusion criteria
1. Age 18 years or above
2. Ability to provide informed consent.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at time of screening
4. Life expectancy of at least 6 months
5. Histological diagnosis of primary GBM (WHO grade IV)
6. CMV-positive serology or positive staining for CMV in tumour tissue
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Markers of active HBV, HCV, HIV, HTLV I and II or syphilis infection* (presence of HbsAg, HCV antibody, HIV antibody, antibodies to HTLV I and II and positive serological test for syphilis, or positive nucleic acid testing [NAT] for HIV, HBV or HCV)
2. Significant non-malignant disease (e.g. severe cardiac or respiratory dysfunction)
3. Psychiatric, addictive or any conditions that may compromise the ability to participate in this trial, as assessed by the Clinical Investigator
4. Prior cancers, except those diagnosed >5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of <5%, or successfully treated non-melanoma skin cancer, or carcinoma in situ of the cervix.
5. Receiving immunosuppressive therapy, except dexamethasone as given for normal management of symptoms related to the brain tumour and its treatment
6. Women who are pregnant, lactating, or unwilling to use adequate contraception
* N.B. Positive serology for HBV indicating previous but cleared infection with HBV is not an exclusion criterion.

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)
Patients will be identified by the Clinical Investigator based on suspicion of GBM (if the patient is already under the care of the Clinical Investigator), or they will be referred to the Clinical Investigator following diagnosis of GBM. Patients will initially be approached to participate in QIMR Berghofer project P158—a monitoring study for patients with brain tumours. They will be provided with a P158 Participant Information and Consent Form (PICF), and the monitoring study discussed with them. If the patient provides their consent to participate in P158, they will donate blood for testing. The results of these tests may be used as part of the screening required for this trial if the patient is later confirmed to have GBM and agrees to participate in the trial.
For patients identified prior to surgery, tumour type will be determined by an accredited pathology laboratory via analysis of the removed tumour specimen. In cases where the patient is confirmed to have both GBM and CMV, they will be provided with the PICF for this clinical trial. This form describes the purpose of the study, the procedures to be followed, and the risks and benefits of participation. Also discussed in this form is the possibility that no direct or immediate benefit may be achieved by this therapy, and that unforeseen toxicity may occur, which will be treated unconditionally at the attending hospital. The Clinical Investigator will conduct the informed consent discussion, answer any questions about the study, and check that the participant comprehends the information provided. Consent will be voluntary and free from coercion.
The Investigator who conducts the consent discussion will also sign the PICF, attesting that they have provided the relevant explanation. A copy of the signed form will be given to the participant.
Each participant will undergo further screening which will involve a clinical evaluation, recording of medical history, and an ECOG performance scale assessment. In addition, up to 30 mL of blood will be collected for further assessments, to be completed by an accredited pathology laboratory. If a participant is screened and does not meet the eligibility criteria for the trial, they will be notified by telephone. Participants who meet the eligibility criteria following screening will be notified that they are formally enrolled, and an appointment will be made for the collection of blood for therapy generation. A 250–300 mL blood sample will be collected to generate CMV-specific T cells for up to six adoptive transfers of T cells. Once these cells have passed quality assurance assessment, treatments will be scheduled.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable, single group, non-randomised study
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
none
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
With an expected drop-out rate of 10% and a sample size of 20, the effective sample size will be 18. Power calculations are generated based on the effective sample size of 18.

The probability of observing at least one participant experience an AE in a sample of 18 participants receiving the investigational product (including 10% dropout) is 0.98, if the probability of that event occurring is assumed to be 0.2. If the proportion of people who experience an AE is >0.5, we will be
able to say with 80% power and 5% statistical significance, that the probability of an AE is >0.1.

Any missing data will be obtained from source documents. Where such data are not available, statistical methods will be employed to ensure that a valid statistical analysis can still be performed. For example, summary statistics will be used for each participant. Any changes or deviations from the original statistical plan will be described and justified in the Clinical Study Report. Every attempt will be made to avoid any deviations from the original statistical plan.

No interim analysis is planned for this study. Twenty participants who have received at least two adoptive transfers of the investigational product will be used in the statistical analysis. When a participant receives less than two adoptive transfers of the investigational product, they will be recorded as having withdrawn from the study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/06/2015
Actual
30/07/2015
Date of last participant enrolment
Anticipated
1/06/2017
Actual
21/11/2017
Date of last data collection
Anticipated
2/07/2018
Actual
21/05/2019
Sample size
Target
20
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 9621 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 291191 0
Charities/Societies/Foundations
Name [1] 291191 0
QIMR Berghofer Medical Research Institute
Country [1] 291191 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] 289871 0
None
Name [1] 289871 0
Address [1] 289871 0
Country [1] 289871 0
Other collaborator category [1] 278447 0
Individual
Name [1] 278447 0
Professor David Walker
Address [1] 278447 0
Managing Director and Neurosurgeon
The Newro Foundation
Level 10, Evan Thompson Building
The Wesley Hospital, 24 Chasely St, Auchenflower Qld 4066
Country [1] 278447 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292763 0
QIMR Berghofer Human Research Ethics Committee
Ethics committee address [1] 292763 0
Ethics committee country [1] 292763 0
Australia
Date submitted for ethics approval [1] 292763 0
Approval date [1] 292763 0
24/04/2015
Ethics approval number [1] 292763 0
P2105
Ethics committee name [2] 292764 0
Uniting Health Care HREC
Ethics committee address [2] 292764 0
Ethics committee country [2] 292764 0
Australia
Date submitted for ethics approval [2] 292764 0
Approval date [2] 292764 0
Ethics approval number [2] 292764 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56846 0
Prof Rajiv Khanna
Address 56846 0
Director, QIMR Centre for Immunotherapy and Vaccine Development
Head Tumour Immunology Laboratory
CBCRC, Level 10, QIMR Berghofer, 300 Herston Rd, Herston Qld 4006
Country 56846 0
Australia
Phone 56846 0
+61 7 3362 0385
Fax 56846 0
Email 56846 0
Rajiv.Khanna@qimrberghofer.edu.au
Contact person for public queries
Name 56847 0
Michelle Neller
Address 56847 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston Qld 4006
Country 56847 0
Australia
Phone 56847 0
+61 7 3362 0412
Fax 56847 0
+61 7 3845 3510
Email 56847 0
immunotherapy@qimrberghofer.edu.au
Contact person for scientific queries
Name 56848 0
Rajiv Khanna
Address 56848 0
Director, QIMR Centre for Immunotherapy and Vaccine Development
Head Tumour Immunology Laboratory
CBCRC, Level 10, QIMR Berghofer, 300 Herston Rd, Herston Qld 4006
Country 56848 0
Australia
Phone 56848 0
+61 7 3362 0385
Fax 56848 0
Email 56848 0
Rajiv.Khanna@qimrberghofer.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAutologous CMV-specific T cells are a safe adjuvant immunotherapy for primary glioblastoma multiforme.2020https://dx.doi.org/10.1172/JCI138649
Dimensions AICytomegalovirus and Glioblastoma: A Review of the Biological Associations and Therapeutic Strategies2022https://doi.org/10.3390/jcm11175221
Dimensions AICytomegalovirus-Specific Immunotherapy for Glioblastoma Treatments2022https://doi.org/10.14791/btrt.2022.0010
N.B. These documents automatically identified may not have been verified by the study sponsor.