Chimeric Antigen Receptor (CAR)-T Cells to Target GD2 for Diffuse Midline Glioma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP
研究概览
简要总结
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.
详细描述
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 ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with GD2CAR vector to generate GD2CAR T-cells.
Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate.
Patients will have an intraventricular catheter (Ommaya catheter) placed following enrolment and prior to GD2 CAR T cell infusion to allow monitoring, and treatment if necessary, of increased intracranial pressure (ICP).
Patients will receive lymphodepleting (LD) chemotherapy with fludarabine 30mg/m2 administered over 4 days (Day -6 to Day -3) and cyclophosphamide 60mg/kg administered over 2 days (Day -4 and Day-3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 2 and ≤ 16 years
- •Tissue diagnosis of H3K27M mutant Diffuse Midline Glioma.
- •Radiographically evident tumour restricted to the brain stem or spinal cord.
- •At least 6 weeks following completion of radiation therapy.
- •At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial
- •Performance status: Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≥ 40% allowing for stable neurological deficit due to DMG
- •Absolute neutrophil count ≥1.5 x109/L and platelet count ≥ 100 x109/L
- •Total bilirubin < 1.5 ULN and ALT < 2.5 ULN
- •Serum creatine < 1.5 ULN for age.
- •For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable)
- •Written informed consent
排除标准
- •Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of RQR8/huK28Z CAR T cell infusion
- •Tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed)
- •Clinical or radiological evidence of true tumour progression
- •Active hepatitis B, C or HIV infection
- •Inability to tolerate leukapheresis
- •Pre-existing significant neurological disorder not related to DMG
- •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.
- •Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC
- •Any contraindication to the use of Anticoagulant Citrate Dextrose Solution
- •Any contraindication to Ommaya reservoir insertion (or similar catheter)
- •Known allergy to albumin, DMSO or EDTA
- •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
- •Prior treatment with investigational or approved gene therapy or cell therapy products
- •Life expectancy <3 months
- •Use of rituximab (or rituximab biosimilar) within the last 3 months prior to RQR8/huK28Z CAR T cell infusion
- •Post-pubertal subjects who are pregnant or breastfeeding
研究组 & 干预措施
GD2 CAR T Cells
Treatment with the ATIMP: GD2 CAR T-cells
干预措施: GD2 CAR T cells (Biological)
结局指标
主要结局
Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP
时间窗: 28 days
Toxicity of GD2 CAR T cells as assessed by the incidence of grade 3-5 toxicity causally related to the ATIMP (particularly severe cytokine release syndrome and severe neurotoxicity).
Feasibility of manufacturing GD2 CAR T-cells evaluated by the number of therapeutic products generated
时间窗: 28 days
Feasibility of generation of the ATIMP as evaluated by the number of therapeutic products generated and the number of ATIMPs infused (as an intravenous agent (Theme 1) and as an intraventricular agent (Theme 2) after successful manufacture.
次要结局
- Overall survival (OS)(1 year)
- Progression Free Survival (PFS)(1 year)
- Time to Progression (TTP)(1 year)
- Best objective response rate (ORR)(1 year)