T cells and pembrolizumab for recurrent and newly diagnosed glioblastoma
- Conditions
- Glioblastoma multiforme/astrocytoma grade 4Cancer - Brain
- Registration Number
- ACTRN12623001126606
- Lead Sponsor
- QIMR Berghofer Medical Research Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 58
1. Participants who are at least 18 years of age on the day of signing informed consent with
histologically confirmed diagnosis of GBM or astrocytoma Grade 4.
a. For participants with recurrent GBM or astrocytoma grade 4, histological confirmation of
primary diagnosis is available
i. First occurrence of disease progression with radiological confirmation greater than or equal to 12 weeks from completion of radiation therapy.
ii. Where surgical resection of recurrent disease occurred, histological confirmation of GBM or
astrocytoma Grade 4 is required.
b. For participants with newly diagnosed GBM or astrocytoma Grade 4, histological confirmation of diagnosis is required
i. Participant, in consultation with their treating clinicians, is willing to delay the
commencement of standard of care adjuvant temozolomide until the completion of CMV-specific T cell therapy infusions.
Note: Participant eligibility will not be dependent on IDH status. Histological confirmation using the 2016 or 2021 WHO Classification of Tumours of the CNS is acceptable and
classification edition will be noted.
2. Male participants:
A male participant must agree to use a contraception as detailed in the protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
3. Female participants:
A female participant is eligible to participate if she is not pregnant, not
undergoing in vitro fertilisation and not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
OR
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at 120 days after the last dose of study treatment.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. Approved interpreters will be used for patients who do not have sufficient understanding of English for informed consent to be obtained without an interpreter.
5. Participants who have AEs due to previous anti-cancer therapies must have recovered to less than or equal to Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have less than or equal to Grade 2 neuropathy are eligible. Participants with greater than Grade 1 AE(s) due to previous anti-cancer therapies may be allowed to enrol on a case-by-case basis in discussion with the study Sponsor, if it is determined that it will not put the participant at a higher risk of study-related AEs or interfere with the integrity of the study outcome.
6. For participants with disease progression, this should be the first evidence of measurable disease based on modified RANO criteria. Lesions situation in a previously irradicated area are considered measurable if progression has been demonstrated in such lesions.
7. CMV-positive serology
8. Provision of consent for the use of archival formalin-fixed, paraffin embedded (FFPE) or fresh tumour tissue obtained at the time of surgical resection or excisional biopsy.
Note: Clinical outcome predictors IDH1/2, MGMT status, ATRX, EGFR amplification and Ki-67 not available at screening will be analysed following the completion of recruitment.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study inter
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
3. Has received prior systemic anti-cancer therapy or investigational agents within 4 weeks prior to study intervention, with the exception of temozolomide, which is permitted during the trial.
4. Participants enrolled with recurrent disease must have recovered from all radiation-related toxicities not require corticosteroids (other than dexamethasone) and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (less than or equal to 2 weeks of radiotherapy) to non-CNS disease.
Note: Participants receiving dexamethasone must be clinically stable and receiving a stable or weaning dose of less than or equal to 2mg/day 1–2 weeks prior to the commencement of pembrolizumab
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines is allowed.
6. Has received in an investigational agent, or has used an investigational device within 4 weeks prior to the first dose of study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Known additional malignancy that is progressing or has required active treatment within the past 5 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, prostate cancer treated with radical prostatectomy, or carcinoma in situ, excluding carcinoma in situ of the bladder, who have undergone potentially curative therapy are not excluded.
Participants with additional malignancy within the past 5 years may be allowed to enrol on a case-by-case basis, in discussion with the study Sponsor, if the malignancy is deemed of very low recurrence potential and the participant has completed curative intent therapy.
9. Has a previous known GBM/astrocytoma grade 4 recurrence previously treated with surgery, radiotherapy and/or chemotherapy, and evidence of further progression or recurrence.
10. Has severe hypersensitivity (greater than or equal to Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid).
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of human immunodeficiency virus (HIV) infection.
Note: No HIV testing is required unless mandated by a local health authority.
15. Concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
Note: Hepatitis B and C screening tests are not required unless:
• Known history of HBV and HCV infection
• As mandated by local health authority
1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method