NCT00091104已完成1 期
A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 4
- 主要终点
- Safety
研究概览
简要总结
RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.
详细描述
OBJECTIVES:
Primary
- Determine the safety of peripheral blood lymphocytes (PBLs) retrovirally transduced with an anti-MART-1 T-cell receptor (TCR) gene followed by high-dose aldesleukin (IL-2) and MART-1:27-35 peptide vaccine in patients with HLA-A*0201-positive metastatic melanoma receiving a myeloablative preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation.
- Determine, preliminarily, whether antitumor antigen TCR-engineered tumor-infiltrating lymphocytes or PBLs followed by IL-2 and MART-1:26-35 after a nonmyeloablative but lymphoid-depleting preparative regimen will result in clinical tumor regression in these patients.
Secondary
- Determine the in vivo survival of TCR gene-engineered cells from these patients.
- Evaluate, preliminarily, clinical response in these patients.
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:
- •Diagnosis of metastatic melanoma
- •HLA-A*0201-positive disease
- •Measurable disease
- •Refractory to standard therapy, including high-dose aldesleukin therapy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •More than 3 months
- •Hematopoietic
- •Absolute neutrophil count > 1,000/mm^3
- •Platelet count > 100,000/mm^3
- •Hemoglobin > 8.0 g/dL
- •Lymphocyte count > 500/mm^3
- •WBC > 3,000/mm^3
- •No coagulation disorder
- •ALT and AST < 3 times upper limit of normal
- •Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL for patients with Gilbert's disease)
- •Hepatitis B antigen negative
- •Hepatitis C antibody negative (unless antigen negative)
- •Creatinine ≤ 1.6 mg/dL
- •Cardiovascular
- •No myocardial infarction
- •No cardiac arrhythmias
- •No cardiac ischemia
- •LVEF ≥ 45% by stress cardiac test* (for patients ≥ 50 years of age OR those with a history of EKG abnormalities)
- •No other major cardiovascular illness by stress thallium or comparable test NOTE: *Stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test
- •No major respiratory illness
- •No obstructive or restrictive pulmonary disease
- •FEV_1 ≥ 60% of predicted on pulmonary function test*
- •DLCO ≥ 60% predicted (for total-body irradiation cohort) NOTE: *For patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction
- •Immunologic
- •HIV negative
- •No major immune system illness
- •No active systemic infection or opportunistic infection
- •No primary immunodeficiency (e.g., autoimmune colitis or Crohn's disease)
- •No secondary immunodeficiency (e.g., due to chemotherapy or radiotherapy)
- •No history of severe immediate hypersensitivity reaction to study drugs
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 4 months after completion of study treatment
- •Must sign a durable power of attorney
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •See Disease Characteristics
- •Recovered from prior immunotherapy
- •Prior immunization to melanoma antigens allowed
- •Progressive disease during prior immunization allowed
- •Prior cellular therapy, including vector transduction with or without myeloablation, allowed
- 另有 11 项未显示
排除标准
- 未提供
结局指标
主要结局
Safety
Tumor regression
次要结局
- In vivo survival of transplanted cells
- Clinical response
研究者
研究点 (4)
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