2026-525876-24-00招募中2 期
Phase I/II clinical trial on the use of central nervous system administrations of CART-NKG2D or NKIL15 cells in children, adolescent and young adults with recurrent/refractory high grade Central Nervous System tumours (CINK-CAR)
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence and severity and relatedness of adverse reactions. Incidence of SAEs. Changes of performance status over time. Incidence of IMP-related Grade ≥3 toxicities at day 48. Incidence and grade of CRS (ASTCT) and neurotoxicity/ICANS, including need for ICU, tocilizumab, corticosteroids.
研究概览
简要总结
To determine the safety of the AMTP products NKIL15 and CART-NKG2D when administered loco-regionally in children and young adults with high-grade CNS tumours.
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase I/II, open label, prospective, multi-centre trial with an umbrella design for relapsed/refract
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Age: ≤ 20 years patients suffering from recurrent/refractory CNS tumours including, but not limited, to medulloblastoma (MB), atypical teratoid/rhabdoid tumour (AT/RT), ependymoma or high-grade gliomas involving the brain and/or spine at original diagnosis or relapse. Patients must have recurred or not responded to at least one previous line of chemotherapy, and that according to the treating physician, no other known-curative treatment can be offered. They must have histological verification at diagnosis and/or relapse.
- •Patients with a seizure disorder may be enrolled if well-controlled with anticonvulsants.
- •Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
- •Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the infusion. Male partner should use a condom.
- •Available NKG2DL expression evaluation in tumour tissue.
- •Patients must have either measurable or evaluable tumour. Measurable disease defined as presence of at least one lesion that can be accurately measured in two dimensions, each of which measure at least 10 mm. Evaluable disease is defined as at least one lesion that cannot be accurately measured in at least one dimension, or positive CSF cytology.
- •Patient must be assessed by neurosurgeon to be a candidate to receive ATMP cell infusion either by an ommaya reservoir or intrathecally, whichever is considered the best option for the patient.
- •Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles (ommaya reservoir) to receive ATMP cell infusion (in case of intraventricular infusion).
- •Lansky (age <16 years) or Karnofsky (age >=16 years) score of 50 or greater.
- •Patients must have recovered from the acute toxic effects of all prior anticancer therapy (including chemotherapy and radiotherapy, ≤ grade 2 according to CTCAE v5.0).
- •An interval of at least 12 weeks must have elapsed since the completion of radiation therapy. At least 2 weeks since the completion of any cytotoxic chemotherapy regimen. For targeted agents, a minimum of 2 weeks since the last dose. For patients who have received prior bevacizumab, at least 6 weeks is required before starting study treatment. At least 12 weeks since the completion of any immunotherapies or cell therapies.
- •Adequate bone marrow, hepatic and renal function according to the investigators criteria depending on individual patient status.
排除标准
- •Enrolled in another treatment protocol in the previous 4 weeks.
- •Ventriculoperitoneal (VP) shunt, unless it is programmable and the VP shunt can be turned to the lowest setting before the infusion and until 3 hours after (as determined by the Neurosurgeons).
- •Any other concomitant neoplasia, as well as presence of extra-cranial metastasis.
- •Any concomitant and uncontrolled medical disease.
- •Extensive disease, disease location, and/or co-morbid condition that the PI, the neurosurgeon and/or designee considers unsafe for administration of ATMP infusion.
- •Evidence of untreated and active infection or clinically significant systemic illness: o Cardiac disorder defined as LVEF < 55% determined by ECHO. o Human Immunodeficiency Virus (HIV) positive test. o Presence of active or prior CMV, EBV, hepatitis B or C as indicated by serology. o Any significant pulmonary, hepatic or other organ dysfunction.
- •Active treatment with corticosteroids (except replacement therapy).
- •Evidence of any neurological toxicity grade ≥ 4 (according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0) to previous antitumoural therapies.
- •Pregnant or lactating women.
- •Any other condition that, in the opinion if the investigators, may interfere with the efficacy and/or safety evaluation of the trial.
结局指标
主要结局
Incidence and severity and relatedness of adverse reactions. Incidence of SAEs. Changes of performance status over time. Incidence of IMP-related Grade ≥3 toxicities at day 48. Incidence and grade of CRS (ASTCT) and neurotoxicity/ICANS, including need for ICU, tocilizumab, corticosteroids.
Incidence and severity and relatedness of adverse reactions. Incidence of SAEs. Changes of performance status over time. Incidence of IMP-related Grade ≥3 toxicities at day 48. Incidence and grade of CRS (ASTCT) and neurotoxicity/ICANS, including need for ICU, tocilizumab, corticosteroids.
次要结局
- Progression-free survival (PFS): defined as the time from treatment initiation to disease progression or death from any cause, assessed according to RAPNO and iRECIST criteria. PFS rates will be estimated at 3, 6, and 12 months.
- Overall survival (OS): defined as the time from treatment initiation to death from any cause. OS rates will be evaluated at 3, 6, and 12 months.
- Objective response rate (ORR): defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to RAPNO and iRECIST criteria.
- Duration of response (DoR), defined as the time from the first documented objective response (complete response or partial response according to RAPNO and iRECIST criteria) until disease progression or death from any cause, whichever occurs first.
- Proportion of patients for whom successful manufacturing of NKIL15 or NKG2D-CAR T cells is achieved, defined as production of sufficient cell doses to complete the planned two treatment courses.
- Detection rate of tumour-derived cells in CSF at scheduled study assessments.
- Detection and persistence of NKIL15 cells and NKG2D-CAR T cells in CSF during scheduled assessments.
- Quantification of cytokine levels in CSF samples collected according to the schedule of assessments.
研究者
Antonio Pérez Martínez
Scientific
Hospital Universitario La Paz
研究点 (1)
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