Recurrent/refractory high-grade CNS tumours Cancer
Conditions
Interventions
1. Leukapheresis: Following registration, participants will undergo an unstimulated leukapheresis, which will be used to manufacture the CAR T cells.
2. Ommaya reservoir (or similar catheter) inserti
Sponsors
Cancer Research UK and University College London Cancer Trials Centre
Eligibility
Sex/Gender
All
Age
1 Years to 24 Years
Inclusion criteria
Inclusion criteria: 1. Age: 1.1. UK: =1 and =18 years 1.2. Netherlands: =1 and =24 years 2. Evidence of relapsed or refractory high-grade CNS tumour 3. Exhaustion of standard of care options with curative intent 4. Expression of B7H3 protein in biopsy/resection material obtained either in primary or relapse/refractory setting, measured by immunohistochemistry (IHC), H-score =100 5. Radiographically evaluable disease 6. Negative pregnancy test (if applicable) 7. Agreement to use adequate contraception (if applicable) 8. Written informed consent
Exclusion criteria
Exclusion criteria: Exclusion criteria for trial registration: 1. Bulky disease at time of CAR-T cell infusion 2. Diffuse midline glioma (DMG) 3. Pre-existing significant neurological disorder (other than CNS tumour-related) 4. Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator, is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements 5. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn’s, rheumatoid arthritis, systemic lupus erythematosus) requiring systemic immunosuppression / systemic disease-modifying agents within the last 2 years 6. Any contraindication to Ommaya reservoir (or similar catheter) insertion 7. Inability to tolerate leukapheresis 8. Performance status: Karnofsky (age =10 years) or Lansky (age 60 ml/min/1.73 m² (as per local practice) 17. Coagulation tests (PT and aPTT) outside the local reference ranges (correction with blood products to achieve normal range is permitted) 18. Post-pubertal subjects who are pregnant or breastfeeding 19. Known allergy to DMSO (or any component of the ATIMP) 20. Systemic corticosteroid therapy =0.05 mg/kg dexamethasone daily (or equivalent) at time of CAR-T cell infusion. Corticosteroid physiologic replacement therapy is allowed. Exclusion criteria for first TE9-28z-iTAG2 CAR-T infusion: 1. Bulky disease at time of TE9-28z-iTAG2 CAR-T cell infusion 2. Performance status: Karnofsky (age =10 years) or Lansky (age <10 years) score <50% 3. Uncontrolled fungal, bacterial, viral or other infection 4. Absolute neutrophil count =1.0 x 10e9/L, platelets =50 x 10e9/L, lymphocytes =0.25 x 10e9/L 5. Coagulation tests (PT and aPTT) outside the local reference ranges (correction with blood products to achieve normal range is permitted) 6. Absence of functional Ommaya Reservoir (or similar catheter) in situ. 7. Absence of baseline imaging of tumour performed prior to first CAR-T cell infusion 8. Systemic corticosteroid therapy =0.05 mg/kg dexamethasone daily (or equivalent) at time of CAR-T cell infusion. Corticosteroid physiologic replacement therapy is allowed. 9. Less than 2 weeks following completion of standard-of-care radiotherapy or systemic anti-cancer treatment. 10. Less than 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents in any other early-phase clinical trial. Exclusion criteria for subsequent CAR-T cell infusions: 1. Occurrence of dose-limiting toxicities (DLT) with prior TE9-28z-iTAG2 CAR-T cell infusions. In patients in dose levels 2 or 3 who experience a DLT, subsequent CAR-T infusions may be given at the next lowest dose level if the patient has fully recovered from the toxicity. 2. Uncontrolled fungal, bacterial, viral or other infection 3. Imaging evidence of progressive disease following previous TE9-28z-iTAG2 CAR-T infusion 4. Systemic corticosteroid therapy =0.05 mg/kg dexamethasone daily (or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety: toxicity of TE9-28z-iTAG2 CAR-T cells as assessed by the incidence of grade 3-5 toxicity causally related to the ATIMP (particularly severe CRS and severe neurotoxicity) occurring within 28 days of the first TE9-28z-iTAG2 CAR-T cell infusion 2. Feasibility of generation of TE9-28z-iTAG2 CAR-T cells at specified dose levels as evaluated by the number of therapeutic products generated for that dose level and the number of ATIMPs infused intracerebroventricularly after successful manufacture | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Incidence and severity of adverse events recorded during at any period following Day 0 of ATIMP infusion 2. Clinical outcomes, including overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and time to progression (TTP), after ICV TE9-28z-iTAG2 CAR-T cell infusion: 2.1. OS: time from CAR T infusion to death by any cause 2.2. PFS: time from CAR T infusion to progressive disease (PD) or death 2.3. TTP: time from the first ATIMP infusion to PD or death attributed to the underlying CNS tumour, whichever occurs first 3. Clinical and radiographic response after ICV TE9-28z-iTAG2 CAR-T cell infusion: time of achieving best response (complete response [CR], partial response [PR]) at 28 days, 3 months, and 6 months following the first ATIMP infusion. | — |
Countries
England, Netherlands, United Kingdom
Contacts
Public ContactCARTUNE Trial Manager
Outcome results
None listed