Phase I/II Study To Evaluate The Safety Of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following CD25 Lymphodepletion For Patients With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- In vivo survival of CD8+ transferred T-clones
研究概览
简要总结
RATIONALE: White blood cells that have been treated in a laboratory may be able to kill tumor cells in patients with melanoma. Aldesleukin and denileukin diftitox may stimulate the white blood cells to kill melanoma cells. Giving therapeutic autologous lymphocyte therapy together with aldesleukin and denileukin diftitox may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving therapeutic autologous lymphocytes together with aldesleukin and denileukin diftitox and to see how well it works in treating patients with stage III-IV melanoma
详细描述
PRIMARY OBJECTIVES:
I. Assess the safety of cellular adoptive immunotherapy in melanoma patients using autologous CD8+ antigen-specific T-cell clones following CD25 lymphodepletion.
II. Determine the influence of CD25 lymphodepletion on the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell (CTL) clones.
SECONDARY OBJECTIVES:
I. Assess the anti-tumor efficacy of cellular adoptive immunotherapy in melanoma patients using autologous CD8+ antigen-specific T cell clones following CD25 lymphodepletion.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathological documentation of melanoma
- •Expression of human leukocyte antigen (HLA)-A2 or B44 as determined by HLA typing lab
- •Patients whose tumor expresses targeted antigen and restricting allele against which CD8 T cell clones can be generated
- •Karnofsky Performance status of at least 80% and an expected survival of greater than 6 months
- •Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
- •Normal cardiac stress test (treadmill, echocardiogram, or myocardial perfusion scan) within 182 days prior to enrollment is required of patients with a history of cardiac disease
- •Pulse > 45 or < 120
- •Weight >= 45 kg
- •Temperature =< 38C (< 100.4 F)
- •White blood cells (WBC) >= 3,000
- •Hematocrit (HCT) >= 30%
- •Platelets >= 100,000
- •Patients must be willing and able to discontinue the use of all antihypertensive medications 24 hours prior to and during IL2 therapy
排除标准
- •Pregnant women, nursing mothers, or women of reproductive ability who are unwilling to use effective contraception or abstinence
- •Serum creatinine > 1.6mg/dL
- •Creatinine clearance < 75 ml/min
- •Aspartate aminotransferase (AST) > 2.5 x upper limit of normal
- •Alanine aminotransferase (ALT) > 2.5 x upper limit of normal
- •Bilirubin > 1.6 or international normalized ratio (INR) > 1.5 due to hepatic dysfunction
- •Albumin < 3.0g/dL
- •Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with Forced expiratory volume in one second (FEV1) < 80% predicted or diffusing capacity of the lung for carbon monoxide (DLco) (corr for hemoglobin [Hgb]) < 75% will be excluded
- •Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, symptoms of coronary artery disease
- •Symptomatic central nervous system (CNS) metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1cm brain/CNS metastases without significant edema may be considered for treatment
- •Patients with active infections or oral temperature > 38.2 C within 48 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
- •Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy)
- •Concurrent treatment with steroids
- •Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
- •The following agents are not allowed while on study: systemic corticosteroids (except as outlined for management of toxicity of nontransduced CTL), immunotherapy (for example, interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, expanded polyclonal TIL or LAK therapy), pentoxifylline, or other investigational agents
结局指标
主要结局
In vivo survival of CD8+ transferred T-clones
时间窗: Days +0, 1, 3, 7, 14, 22, 28, 29, 31, 35, 42, 49, 56, 63, 70, 77, 84
The design of this trial using the first infusion of CD8 T cells administered alone as a baseline for each patient permits intra-patient analysis using paired samples with increased statistical power.
次要结局
未报告次要终点
研究者
Sylvia Lee
Research Associate
Fred Hutchinson Cancer Center