A trial to test CAR-T cells for glioblastoma in adults when standard treatment is not effective or stops working

Trial ID: ISRCTN22366199

Other - Phase 1 - Recruiting

Background and study aims Glioblastoma is the most common type of brain tumour and despite continued research, remains incurable with little improvement in clinical outcomes over the last three decades. Current treatment for glioblastoma includes surgery, radiotherapy and chemotherapy. While these treatments can be successful in the short term, cancer often returns or progresses (increases) within a year. New treatments for glioblastoma are urgently needed. The CARGO trial will treat glioblastoma patients with a form of CAR-T cells called CARGO-T cells if standard treatment has failed or their cancer has returned. CAR-T cells are T cells (a type of white blood cells) genetically modified in a lab to target tumour cells. In leukaemia and myeloma, CAR-T cells have shown promising results, and several products are now NHS approved. CARGO-T cells target the mutated protein EGFRvIII which can be found on glioblastoma tumour cells in some patients. The trial is a phase I, dose finding and safety study. This means the treatment has never been studied before in this disease and a safe or effective dose is unknown. CARGO will test whether CARGO-T cells can be successfully manufactured and used to treat GBM. Who can participate? Adults aged 16+ with glioblastoma that has not responded to or has returned following standard treatments. In order to be considered for this trial you must reside in the UK and be eligible for NHS care. What does the study involve? The initial study procedure is confirming EGFRvIII tumour positivity via a biopsy. If eligibility is confirmed, participants will undergo an insertion of an Ommaya reservoir (or similar catheter) for monitoring intracranial pressure and possible ICV CARGO-T cells administrations, procurement of starting material for the CARGO-T cells and treatment to control disease whilst the CARGO-T cells are being manufactured. This treatment may include proton beam therapy. Once the CARGO-T cells are manufactured, patients will be given lymphodepletion in preparation for the IV CARGO-T cells infusion. Up to 4 ICV CARGO-T cells infusions may be given if disease does not respond to or returns following the previous infusion. Participants will be followed up for up to 15 years following their last infusion. What are the possible benefits and risks of participating? Benefits: There may be no benefit in taking part in this study. If the CARGO-T cells ‘work’, which is not yet known, this may help shrink the tumour or stop it from growing. The information we receive from those taking part in the study may help improve our knowledge of treating glioblastoma which may benefit the treatment of patients with high-grade gliomas, including glioblastoma, in the future. Risks: This patient population has exhausted standard treatments and the largest risk they face is disease progression. The main risk of participating on the trial is the side effects of the interventions. Neurological side effects such as seizures, headaches and cognitive changes may be experienced. Immune-related side effects are also possible such as increased infections, flu-like symptoms and autoimmune reactions. The surgical procedures carry similar risks to any surgery such as infection and bleeding with the additional possibility of neurological side effects. Participants will be closely monitored, and treatment/supportive care provided where necessary. Where is the study run from? University College London (UK) When is the study starting and how long is it expected to run for? May 2024 to June 2034 Who is funding the study? Jon Moulton Charity Trust (UK) Who is the main contact? Tushhar Dadaga, ctc.cargo@ucl.ac.uk

Conditions

• Relapsed/refractory glioblastoma
• Cancer

Interventions

• CARGO-T cells [INN not proposed yet]

Eligibility

Inclusion criteria

• 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

Exclusion criteria

• Current key exclusion criteria as of 20/01/2026: 1. ECOG 3 - 4 2. Metastatic or primary spinal GBM 3. Organ function: 3.1. Cardiac: Serious and uncontrolled cardiac arrhythmias 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 <50 ml/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 >4 mg dexamethasone (or equivalent) daily 12. Women who are pregnant or breastfeeding _____ Previous key exclusion criteria: 1. ECOG 3 - 4 2. Metastatic or primary spinal GBM 3. Organ function: 3.1. Cardiac: Serious and uncontrolled cardiac arrhythmias 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 <50 ml/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 >2 mg dexamethasone (or equivalent) daily 12. Women who are pregnant or breastfeeding

Sponsor

University College London

Source: https://www.isrctn.com/

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