NCT03344250已完成1 期
A Phase I Study Targeting Newly Diagnosed Glioblastoma with Anti-CD3 × Anti-EGFR Bispecific Antibody Armed T Cells (EGFR BATs) in Combination with Radiation and Temozolomide
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy.
详细描述
In addition to finding the safe dose of EGFR BATs, immune evaluations will be performed as delineated in the schedule of events to measure immune responses during all stages of treatment for GBM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed newly diagnosed intracranial GBM or gliosarcoma
- •Age ≥ 18 years.
- •Karnofsky Performance Status ≥
- •Be willing and able to provide written informed consent for the trial.
- •For patients with resection, CT/MRI with contrast must be performed within 72 hours following resection. Intraoperative post resection MRI is acceptable. No post surgery CT/MRI is required for patients who have received biopsy.
- •Females of childbearing potential, and males, must be willing to use an effective method of contraception
- •Females of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days prior to apheresis.
- •Absolute lymphocyte count ≥ 500/mm3, Absolute neutrophil count (ANC) ≥1,000 /mcL, Platelets ≥ 100,000 / mcL, Hemoglobin ≥ 9 g/dL (or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment), BUN ≤ 1.5 X upper limit of normal (ULN), Serum creatinine within the normal limits OR Measured or calculated creatinine clearance ≥60 mL/min/1.73m2, Serum total bilirubin ≤ 1.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 X ULN, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- •i. Additional inclusion criteria for sub-cohort: MGMT unmethylated according to UVA pathology testing
排除标准
- •Patients with a diagnosis of another malignancy within 3 years of being on-study. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patients must not be on any treatment for another malignancy.
- •Patients with evidence of leptomeningeal dissemination or subependymal spread on initial MRI.
- •Patients with extracranial metastases.
- •Known hypersensitivity to cetuximab or other EGFR antibody.
- •Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range (indicating likely hypersensitivity to cetuximab)
- •Evidence of active bleeding or bleeding diathesis.
- •Cardiac Status: Patients will be ineligible for treatment on this protocol if (prior to protocol entry):
- •There is a history of a recent (within one year) myocardial infarction or stroke.
- •There is a current or prior history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO).
- •There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results).
- •Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- •Has received a live vaccine within 30 days of planned start of study therapy.
- •Has received any treatment for GBM besides surgery.
- •Females must not be breastfeeding.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •A patient may be excluded if, in the opinion of the treating clinician, the patient is not capable of being compliant.
研究组 & 干预措施
Main Study
Experimental
Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. Participants will receive the first and second infusions of EGFR BATs on days 14 and 21 after finishing concurrent RT and TMZ and then receive an infusion on day 21 of the first six cycles of TMZ.
干预措施: EGFR BATs with TMZ following SOC RT/TMZ (Drug)
Subcohort for MGMT unmethylated patients
Experimental
Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. About 4 weeks after completion of RT/TMZ, participants will receive 8 weekly doses of EGFR BATs.
干预措施: Weekly EGFR BATs following SOC RT/TMZ (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: The study will not advance to the next dose until 7 days after the last patient in the cohort completes his or her second infusion of EGFR BATs
Maximum tolerated dose will be based on number of dose limiting toxicities at each dose level
次要结局
- Adverse events, including dose limiting toxicities(Through 30 days following last dose of EGFR BATs)
- Immune measures in blood- anti-GBM antibodies(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Survival(Every 3 months following last study visit until death or study closure, expected within 5 years)
- Response Rate(Every 3 months following last study visit until death or study closure, expected within 5 years)
- Immune measures in blood- interferon-γ(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Immune measures in blood- EliSpots(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Correlation of pathology to PFS and OS(Up to 12 months after study treatment completion)
- Correlation of immune response to PFS and OS(Up to 12 months after study treatment completion)
- Immune measures in blood- serum cytokine patterns(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Immune measures in blood- anti-GBM cytotoxicity of peripheral blood mononuclear cells directed at GBM cell lines(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Correlation of imaging to PFS and OS(Up to 12 months after study treatment completion)
- Immune measures in blood- cellular phenotype(Before surgery (optional), during screening, at apheresis, at multiple timepoints during study treatment, following completion of study treatment, and every 2-6 months after completion of EGFR BATs infusions through 1 year after last EGFR BATs infusion)
- Clinical response(Every 3 months following last study visit until death or study closure, expected within 5 years)
- Correlation of clinical response to PFS and OS(Up to 12 months after study treatment completion)
研究者
Camilo E. Fadul, MD
Professor
University of Virginia
研究点 (1)
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