NCT01212887终止1 期
A Cancer Research UK Phase I Trial of Adoptive Transfer of Autologous Tumor Antigen-Specific T Cells With Preconditioning Chemotherapy and Intravenous IL2 in Patients With Advanced CEA Positive Tumors
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival
研究概览
简要总结
RATIONALE: Placing a gene into T cells may improve the body's ability to recognize cancer cells and build an immune response to fight cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving specially treated T cells together with cyclophosphamide, fludarabine phosphate, and aldesleukin may kill more tumor cells.
PURPOSE: This phase I clinical trial is studying the side effects and best dose of treated T cells when given together with cyclophosphamide, fludarabine phosphate, and aldesleukin in treating patients with cancer.
详细描述
OBJECTIVES:
Primary
- To evaluate the feasibility of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes in combination with preconditioning chemotherapy comprising cyclophosphamide and fludarabine phosphate plus aldesleukin in patients with CEA-positive tumors.
- To assess the toxicity of this regimen in these patients.
- To determine the dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes required to give optimal survival of these cells in the circulation (recommended phase II dose).
Secondary
- To assess whether MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes isolated from the circulation are functional.
- To determine the preliminary tumor response to MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.
- To evaluate the safety of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignancy
- •Metastatic or unresectable disease
- •Standard curative or palliative measures do not exist, are no longer effective, have been completed, or have been refused
- •CEA-positive tumor (either by immunohistochemistry or as demonstrated by elevated CEA > 50 μg/L)
- •No primary brain tumor or brain metastases
- •PATIENT CHARACTERISTICS:
- •WHO performance status 0-1
- •Life expectancy ≥ 3 months
- •Hemoglobin ≥ 10 g/dL
- •Platelet count ≥ 100 x 10^9/L
- •Neutrophil count ≥ 2.0 x 10^9/L
- •Lymphocyte count ≥ 1.0 x 10^9/L
- •Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT/AST ≤ 5 times ULN
- •Alkaline phosphatase ≤ 5 times ULN
- •Calculated creatinine clearance OR isotope clearance measurement ≥ 50 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception 4 weeks prior to, during, and for 6 months after completion of study therapy (male patients must use barrier-method contraception)
- •LVEF ≥ 50% on MUGA scan (for patients receiving cyclophosphamide)
- •ECG and exercise ECG (or stress ECHO) normal (may be abnormal but not clinically significant)
- •Urine dipstick normal (may be abnormal but not clinically significant)
- •No medical high risk due to nonmalignant systemic disease including active uncontrolled infection
- •No known serologically positive hepatitis B, hepatitis C, HIV, or HTLV
- •No history of autoimmune disease
- •No inflammatory bowel disease
- •No concurrent congestive heart failure or prior history of NYHA class III-IV cardiac disease
- •No concurrent malignancies originating from other primary sites, except for adequately treated cone-biopsied carcinoma in situ of the cervix uteri or basal cell or squamous cell carcinoma of the skin
- •No other condition that, in the investigator's opinion, would make the patient an unsuitable candidate for the clinical trial
- •PRIOR CONCURRENT THERAPY:
- •At least 30 days since prior and no concurrent participation in another clinical trial
- •At least 4 weeks since prior and no concurrent radiotherapy (except for palliative reasons [i.e., control of bone pain])
- •At least 4 weeks since prior and no concurrent endocrine therapy, immunotherapy, or chemotherapy (6 weeks for nitrosoureas and mitomycin C)
- •No toxic manifestations of previous treatment, except for alopecia or certain grade 1 toxicities that, in the opinion of the investigator and CRUK (Cancer Research UK), would exclude the patient (e.g., grade 1 neuropathy or grade 1 fatigue)
- •No prior major thoracic and/or abdominal surgery from which the patient has not yet recovered
- •No prior bone marrow transplant or extensive radiotherapy to > 25% of bone marrow
- •No concurrent systemic steroids or other immunosuppressive therapy
- •No other concurrent anticancer therapy or investigational drugs
排除标准
- 未提供
结局指标
主要结局
Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival
Adverse event according to CTCAE version 3 criteria
Dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes that gives the highest frequency in the circulation as measured by the primary assays (recommended phase II dose)
次要结局
- Presence of cells with a functional chimeric immune receptor on bCEA binding assay
- Partial response or complete response on CT scans at 6, 12, 24, and 52 weeks as defined by RECIST criteria
- Long-term follow up for insertional mutagenesis
研究者
研究点 (2)
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