Chimeric Antigen Receptor (CAR)-T Cells to Target GD2 for Diffuse Midline Glioma

Trial ID: NCT05544526

Interventional - Phase 1 - Recruiting

The CARMIGO Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults aged 2-16 years with Diffuse Midline Glioma (DMG). The study will evaluate the feasibility of generating the ATIMP, the safety and tolerability of the GD2CAR T-cell therapy and how effectively GD2CAR T-cells engraft, expand and persist following administration in patients with DMG.

Conditions

• Diffuse Midline Glioma, H3 K27M-Mutant

Interventions

• GD2 CAR T cells

Eligibility

Inclusion criteria

• 1. Age ≥ 2 and ≤ 16 years
• 2. Tissue diagnosis of H3K27M mutant Diffuse Midline Glioma.
• 3. Radiographically evident tumour restricted to the brain stem or spinal cord.
• 4. At least 6 weeks following completion of radiation therapy.
• 5. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial
• 6. Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≥ 40% allowing for stable neurological deficit due to DMG
• 7. Absolute neutrophil count ≥1.5 x109/L and platelet count ≥ 100 x109/L
• 8. Total bilirubin \< 1.5 ULN and ALT \< 2.5 ULN
• 9. Serum creatine \< 1.5 ULN for age.
• 10. For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable)
• 11. Written informed consent

Exclusion criteria

• 1. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of RQR8/huK28Z CAR T cell infusion
• 2. Tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed)
• 3. Clinical or radiological evidence of true tumour progression
• 4. Active hepatitis B, C or HIV infection
• 5. Inability to tolerate leukapheresis
• 6. Pre-existing significant neurological disorder not related to DMG
• 7. 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.
• 8. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC
• 9. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution
• 10. Any contraindication to Ommaya reservoir insertion (or similar catheter)
• 11. Known allergy to albumin, DMSO or EDTA
• 12. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease modifying agents within the last 2 years
• 13. Prior treatment with investigational or approved gene therapy or cell therapy products
• 14. Life expectancy \<3 months
• 15. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to RQR8/huK28Z CAR T cell infusion
• 16. Post-pubertal subjects who are pregnant or breastfeeding

Sponsor

University College, London

Source: ClinicalTrials.gov

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