NCT05353530招募中1 期
Phase I Study -To Assess Safety and Feasibility of IL-8 Receptor Modified Patient-derived Activated CD70 CAR T Cell Therapy in CD70+ Adult GBM and Pediatric High-Grade Gliomas (pHGG)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Safety of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM
研究概览
简要总结
This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in CD70+ adult glioblastoma
详细描述
Newly diagnosed CD70 positive adult GBM patients who have undergone surgery for maximal debulking will be enrolled in this 3+3 design dose-escalation clinical trial and undergo peripheral venipuncture for collection of PBMCs for generation of investigational 8R-70CAR T Cell vaccine. Patients will then undergo standard of care chemoradiation. Immunotherapy will begin 2 weeks (-7/+4 days) after completion of radiation. One single dose of 8R-70CAR T cells will be administered IV. The dose will depend on the enrolling cohort. Dose escalation will follow the traditional 3+3 design.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Adult GBM):
- •Age ≥ 18 years
- •Newly-diagnosed de novo GBM based on the absence of previous history of brain tumor (WHO Grade IV glioma) by histopathology or molecular studies. (secondary GBM not eligible)
- •The tumor must have a supratentorial component
- •CD70 positive (≥5%, 1+)
- •Tumor expression will be scored on a scale of 0 to 3 staining intensity:
- •0 = Negative
- •= Low level
- •= Moderate level
- •= High level
- •The criteria for inclusion will be at least 5% of the cells scoring 1+ staining intensity (> 5%, 1+).
- •Surgical resection of tumors with less than 3cm x 3cm (9 cm2) residual enhancing tumor as a product of longest perpendicular planes by MRI or biopsy only for tumor measuring less than 3cm x 3cm
- •Karnofsky Performance Status (KPS) of > 70%
- •CBC with differential with adequate bone marrow function as defined below:
- •Absolute neutrophil count (ANC) ≥ 1500 cells/mm
- •Platelet count ≥ 100,000 cells/mm
- •Hemoglobin ≥ 10 g/dl. (The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
- •Adequate renal function as defined below:
- •BUN ≤ 25 mg/dl
- •Creatinine ≤ 1.7 mg/dl
- •Adequate hepatic function as defined below:
- •Bilirubin ≤ 2.0 mg/dl
- •ALT ≤ 5 times institutional upper limits of normal for age
- •AST ≤ 5 times institutional upper limits of normal for age
- •Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative.
- •For females of childbearing potential, a negative serum pregnancy test at enrollment.
- •Women of childbearing potential (WOCBP) must be willing to use an acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
- •Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
排除标准
- •(Adult GBM):
- •Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3years. (In situ cancer are permissible)
- •Metastases detected below the tentorium or beyond the cranial vault
- •Leptomeningeal disease beyond the cranial vault. (Focal, adjacent and leptomeningeal involvement is allowable at the discretion of the PI).
- •Recurrent or multifocal malignant gliomas.
- •The patient is not a candidate for cellular therapy as assessed by the study bone marrow transplant physician.
- •Known immunosuppressive disease or human immunodeficiency virus (HIV) infection.
- •Rationale: The need to exclude patients with the immunosuppressive disease or human
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization.
- •Transmural myocardial infarction within the last 6 months.
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the initiation of XRT/TMZ.
- •Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the initiation of XRT/TMZ.
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- •Patients with an autoimmune disease requiring medical management with immunosuppressants.
- •Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
- •Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity.
- •Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant.
- •Patients treated on any other therapeutic clinical protocols within 30 days prior to enrollment.
研究组 & 干预措施
8R-70CAR T cells
Experimental
Cohort 1 will receive 1 x 10^6 cells/kg. Cohort 2 will receive 1 x 10^7 cells/kg. Cohort 3 will receive 1 x 10^8 cells/kg. Cohort 4 will receive Cy/Flu + CAR T cells at established maximum tolerated dose.
干预措施: Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells (Biological)
结局指标
主要结局
Safety of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM
时间窗: 28 days post-infusion
Defined as ≤ 1 DLT out of 6 patients is observed at the 1x10\^8 cells/Kg dose. Dose-Limiting toxicity (DLT) will be defined as any adverse event attributable (possible, probable, or definite) to the administration of 8R-70CAR T cells and occurring from the time of infusion through 28 days post-infusion.
Feasibility of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM
时间窗: 10 weeks
Feasibility will be defined as the ability to infuse 8R-70CAR T-cell safely in 66.7 % of enrolled patients (patients who signed consent and were deemed eligible for the study).
次要结局
未报告次要终点
研究者
研究点 (1)
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