NCT02209376终止1 期
Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
适应症
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Number of adverse events
研究概览
简要总结
An Open-Label Phase 1 Pilot Study to determine the safety and feasibility of CART-EGFRvIII (autologous T cells transduced with a lentiviral vector to express a chimeric antigen receptor specific for EGFRvIII) in the treatment of patients with EGFRvIII+ glioblastoma who have had their first recurrence as determined by standard imaging or have have residual disease after initial resection.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathological criteria: Glioblastoma (GBM) that is histologically confirmed by pathology review of surgically resected tissue.
- •Tumor cells from resected tissue must be available for EGFRvIII testing. Patients who have previously been treated with an EGFRvIII-targeted therapy and recurred, must have a tumor sample obtained after their recurrence available for EGFRvIII testing.
- •Age greater than 18 years.
- •If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.
- •ECOG performance status of 0 or 1 Documented negative serum HCG for female patients of child-bearing potential.
- •Participants with adequate organ function as measured by:
- •White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 9.0 g/dL; without transfusion or growth factor support
- •AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
- •Serum creatinine less than or equal to 1.5 x upper limit of normal
- •Coagulation tests PT and PTT have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
- •Provide voluntary informed consent for Tissue Screening and Apheresis
- •Inclusion Criteria Step 2:
- •Subject met all Step 1 Eligibility Criteria.
- •Tumor cells test positive for EGFRvIII expression (by RT-PCR, next generation sequencing, or immunohistochemistry) and a CART EGFRvIII product has been manufactured and formulated. Patients who have previously been treated with an EGFRvIII-targeted therapy and recurred are only eligible if a tumor sample obtained after their recurrence tests positive for EGFRvIII.
- •Stage of disease:
- •Cohort 1: Patients with first relapse of previously diagnosed primary glioblastoma. Recurrence may be determined by imaging and clinical criteria alone.
- •Cohort 2: Patients with newly diagnosed glioblastoma with a less than 95% resection or greater than or equal to 1 cm^3 of residual disease on the post-operative MRI (typically post-operative day 1).
- •If the patient is on dexamethasone, the dose must be 4 mg/day or less prior to CART-EGFRvIII infusion.
- •It is anticipated that all patients in Cohort 2 will have completed standard of care external beam radiotherapy and chemotherapy with temozolomide (TMZ) at the time of the pre-infusion safety visit.
- •Life expectancy less greater than 3 months
- •ECOG performance status of 0 or 1
- •Participants with adequate organ function as measured by:
- •White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 9.0 g/dL; without transfusion or growth factor support
- •AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
- •Serum creatinine less than or equal to 1.5 x upper limit of normal
- •Coagulation tests PT and PTT have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
- •Adequate cardiac function (greater than EF 55%)
- •Provide voluntary informed consent for study treatment.
- •Female subjects of reproductive potential must agree to use a reliable method of contraception.
- •Exclusion Criteria Step 1:
- •Female subjects of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.
- •Uncontrolled active infection.
- •Active or latent chronic hepatitis B [detectable hepatitis B surface antigen (HBsAg)] or active hepatitis C (positive serology [HCV Ab]) infection.
- •HIV infection.
- •Previous treatment with any gene therapy products.
- •Known addiction to alcohol or illicit drugs.
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- •Exclusion Criteria Step 2:
- •Female subjects of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test within two weeks prior to CART-EGFRvIII cell infusion. The safety of this therapy on unborn children is not known.
- •Uncontrolled active infection.
- •Use of immunosuppressive agents such as cyclosporine, MMF, tacrolimus, or rapamycin within 4 weeks of enrollment on Step
- •A minimal dose of corticosteroid (dexamethasone up to 4 mg/day) is permitted. Recent or current use of inhaled steroids is not exclusionary.
- •Previous treatment with any gene therapy products.
- •Subjects or their physicians anticipate use of any of the following concurrent treatment or medications including: a. Radiosurgery (except for the Standard of Care Fractionated External Radiation therapy is a part of the protocol regimen in Cohort 2) b. Chemotherapy (except for the Standard of Care Temozolomide therapy in Cohort 2) c. Interferon (e.g. Intron-A®) d. Allergy desensitization injections e. Any ongoing investigational therapeutic medication. f. Bevacizumab
- •Participants who have another cancer diagnosis with history of visceral metastases at the time of pre-entry evaluation. The following diagnoses are examples that will be allowed:
- •squamous cell cancer of the skin without known metastasis
- •basal cell cancer of the skin without known metastasis
- •carcinoma in situ of the breast (DCIS or LCIS)
- •carcinoma in situ of the cervix
- •prostate cancer with only PSA recurrence
- 另有 5 项未显示
排除标准
- 未提供
结局指标
主要结局
Number of adverse events
时间窗: 2 years
次要结局
未报告次要终点
研究者
研究点 (3)
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