PHASE I STUDY TO EVALUATE THE SAFETY OF CELLULAR ADOPTIVE IMMUNOTHERAPY USING GENETICALLY MODIFIED AND UNMODIFIED AUTOLOGOUS CD8+ TYROSINASE-SPECIFIC T CELLS FOR PATIENTS WITH METASTATIC MELANOMA
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
研究概览
简要总结
RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.
详细描述
OBJECTIVES:
- Assess the safety and toxicity of cellular adoptive immunotherapy using autologous CD8+ antigen-specific T-cell clones in patients with metastatic melanoma.
- Estimate the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell clones in these patients.
- Evaluate the antitumor effects of CD8+ antigen-specific T-cell clones in these patients.
OUTLINE: Autologous peripheral blood mononuclear cells are harvested and then CD8+ cytotoxic T-lymphocyte (CTL) clones targeting melanosomal antigens are generated ex vivo. Patients receive cellular adoptive immunotherapy comprising autologous CD8+ CTL clones over 30 minutes on day 1. Patients also receive interleukin-2 subcutaneously every 12 hours on days 1-14 of courses 2-3. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed for approximately 1 year after the last infusion.
PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histopathologically proven metastatic melanoma
- •No CNS metastases
- •HLA-A2 positive
- •Bidimensionally measurable disease by palpation on clinical exam or radiographic imaging (x-ray, CT scan, or MRI)
- •Surgically accessible site for tumor cell procurement (skin, subcutaneous nodule, or superficial node) and patient clinically eligible for such surgery
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 80-100%
- •Life expectancy
- •More than 16 weeks
- •Hematopoietic
- •WBC greater than 4,000/mm^3
- •Absolute neutrophil count greater than 2,000/mm^3
- •Platelet count greater than 100,000/mm^3
- •Hematocrit greater than 30%
- •Bilirubin no greater than 1.6 mg/dL
- •SGOT no greater than 150 IU (or no greater than 3 times normal)
- •Prothrombin time no greater than 1.5 times control
- •Creatinine no greater than 2.0 mg/dL
- •Calcium no greater than 12 mg/dL
- •Cardiovascular
- •No congestive heart failure
- •No clinically significant hypotension
- •No symptoms of coronary artery disease
- •No arrhythmia on EKG requiring drug therapy
- •No severe chronic obstructive pulmonary disease
- •FEV_1 at least 1.0 L
- •DLCO at least 45% of predicted
- •No active infection or oral temperature greater than 38.2 degrees C within 72 hours of study
- •No systemic infection requiring chronic maintenance or suppressive therapy
- •HIV negative
- •No history of seizures
- •No retinitis or choroiditis
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use adequate contraception
- •Peripheral blood samples available weekly for 4 consecutive weeks
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •At least 4 weeks since other prior immunotherapy
- •Chemotherapy
- •1 or 2 courses of cytoreductive chemotherapy allowed for bulky disease
- •At least 4 weeks since prior standard or investigational chemotherapy
- •Endocrine therapy
- •At least 4 weeks since prior steroid therapy
- •Radiotherapy
- •At least 4 weeks since prior radiotherapy
- •Not specified
- •At least 4 weeks since other prior investigational drug therapy and recovered
排除标准
- 未提供