A trial to test CAR-T cells for glioblastoma in adults when standard treatment is not effective or stops working
- Conditions
- Relapsed/refractory glioblastomaCancer
- Registration Number
- ISRCTN22366199
- Lead Sponsor
- niversity College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 12
1. Age =16 years
2. Disease status:
2.1. Relapsed or recurrent IDH-wildtype GBM confirmed by pathology review of surgically resected tissue, and
2.2. Tumour tissue is positive for EGFRvIII expression as performed by immunohistochemistry (IHC)
3. Written informed consent (or where applicable, consent by a legal representative)
4. Agree to undergo a pregnancy test and use adequate contraception (where applicable)
Trial inclusion criteria: for radiotherapy:
5. =6 months since completion of primary radiotherapy.
6. Prior history of standard dose, conventionally fractionated brain radiotherapy (i.e. 54 - 60Gy in 28 - 33 fractions).
7. Up to and including three enhancing lesions.
8. Predicted re-irradiation Gross Tumour Volume <50cm³
9. Maximum diameter of enhancing disease must be =6cm
1. ECOG 3 - 4
2. Metastatic or primary spinal GBM
3. Organ function:
3.1. Cardiac: Serious and uncontrolled cardiac arrythmias despite medical management, history of ischemic heart disease within the last 6 months before eligibility confirmation and left ventricular ejection fraction (LVEF) <40%
3.2. Pulmonary: Requirement for supplemental oxygen and/or oxygen saturation =90% on air
3.3. Renal: Creatinine clearance <50ml/min
3.4. Hepatology: Bilirubin >2x upper limit of normal
3.5. Neurologic: Pre-existing significant neurological disorders unrelated to the CNS malignancy investigated in this study
4. Active hepatitis B, C or HIV
5. Active severe infection
6. History of or active medical or psychiatric condition that is uncontrolled with current treatment or deemed by the investigators to be severe enough to preclude participation in this study
7. Unable to undergo leukapheresis due to contraindications, inability to tolerate procedure and/or issues with adequate venous access for the procedure
8. Known allergy to study product excipients (albumin, DMSO, dextran)
9. Cohort 3 only: Any contraindications to receiving ipilimumab including history of clinically significant pneumonitis or lung fibrosis <24 weeks before registration
10. History of auto-immune disease or connective tissue disease requiring systemic immunosuppression/disease-modifying agents within 24 months before registration or resulting in end-organ damage
11. Steroid therapy requiring >2mg dexamethasone (or equivalent) daily
12. Women who are pregnant or breast feeding
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Toxicity following CARGO-T cells administration will be evaluated by the number of grade 3-5 adverse events causally related to the ATIMP at 28 days post ATIMP infusion<br>2. Feasibility of leukapheresis collection and generation of CARGO-T cells as evaluated by the number of therapeutic products generated following ATIMP manufacture<br>3. Feasibility of administration of CARGO-T cells therapy measured by the number of successful CARGO-T cells administrations, firstly as an IV agent (Theme 1) and in the event of non-response/relapse following IV, as an ICV agent, with option for repeated dosing (Theme 2)<br>
- Secondary Outcome Measures
Name Time Method 1. Efficacy will be measured by the proportion of patients achieving responses and depth of response following the RANO 2.0 criteria at 1, 3 and 6 months post ATIMP infusion<br>2. Persistence and frequency of circulating CARGO-T cells in peripheral blood will be assessed by the number of CARGO-T cells in blood samples as per flow cytometry and qPCR at several timepoints between ATIMP infusion to 24 months post infusion<br>3. Relapse rate, progression-free survival and overall survival will be assessed at 12 and 24 months post ATIMP infusion<br>4. The feasibility of proton beam therapy as a bridging therapy will be assessed by the proportion of patients who complete PBT as planned at the time of completion of PBT, and the proportion of patients who then undergo CARGO-T cells administration on Day 0 (infusion)<br>