Treatment of Stage IV Breast Cancer With OKT3 x Herceptin Armed Activated T Cells, Low Dose IL-2, And GM-CSF (Phase I Only as of 4-22-09 as Per IRB Approval Date)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose
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. Combining different types of biological therapies may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of armed activated T cells given in combination with interleukin-2 and sargramostim (GM-CSF) in women with stage IV breast cancer.
- Determine the toxicity profile of this regimen in these patients.
- Determine the clinical response and overall and progression-free survival of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of armed activated T cells.
Patients undergo peripheral blood mononuclear cell (PBMC) collection. The PBMCs are treated ex vivo with monoclonal antibody OKT3 to form armed activated T cells (ATC). The armed ATC are expanded for 14 days in interleukin-2 (IL-2).
Patients receive armed ATC IV over 30 minutes twice weekly for 4 weeks. Patients also receive IL-2 subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first infusion of armed ATC and continuing until 7 days after the last infusion of armed ATC.
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 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed infiltrating ductal carcinoma of the breast
- •Metastatic disease
- •Clinically asymptomatic with non-life-threatening metastases allowed
- •Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone scan, or physical examination
- •No measurable disease allowed if tumor or metastasis has been removed or successfully treated prior to study
- •No rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs and liver)
- •Stable or unstable disease for 3 months on hormonal therapy
- •Stable or unstable disease for at least 1 month after chemotherapy
- •No active brain metastases
- •Brain metastases previously treated with definitive radiotherapy and/or surgical resection allowed
- •Hormone receptor status:
- •Estrogen and progesterone receptor status known
- •All Phase I criteria
- •HER2/neu overexpression (2+ or 3+) by immunohistochemistry
- •Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Menopausal status:
- •Not specified
- •Performance status:
- •Karnofsky 70-100% OR
- •Life expectancy:
- •At least 3 months
- •Hematopoietic:
- •Granulocyte count at least 1,500/mm^3
- •Platelet count at least 50,000/mm^3
- •Hemoglobin at least 8 g/dL
- •Bilirubin less than 1.5 times normal
- •SGOT less than 1.5 times normal
- •Creatinine no greater than 1.8 mg/dL
- •Creatinine clearance at least 60 mL/min
- •BUN no greater than 1.5 times normal
- •Cardiovascular:
- •No myocardial infarction within the past year
- •No prior myocardial infarction with coronary symptoms requiring medication and/or depressed left ventricular function (LVEF less than 50% by MUGA)
- •No angina or coronary symptoms requiring medication and/or with depressed left ventricular function (LVEF less than 50% by MUGA)
- •No congestive heart failure requiring medical management
- •LVEF at least 50% at rest by MUGA
- •No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg)
- •FEV1, DLCO, and FVC at least 50% predicted
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •No other serious medical or psychiatric illness that would preclude study participation
- •No other prior or concurrent malignancy within the past 5 years except curatively treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •See Disease Characteristics
- 另有 11 项未显示
排除标准
- 未提供
研究组 & 干预措施
Aldesleukin, Sargramostim & therapeutic autologous lymphocytes
Peripheral blood mononuclear cells (PBMC) for the generation of ATC will be collected using 1 or 2 phereses to obtain 8-20 × 109 PBMC for T cell expansion. The PBMC will be activated with OKT3 and expanded in IL-2 to generate from 20-320 ×109 ATC during a maximum of 14 days of culture. Three patients will be treated at each dose level. The dose levels for each infusion are: 5, 10, 20, and 40 billion. Each patient will receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encounter toxicities related to armed ATC, the dose and administration will be modified as delineated per the protocol. The patients will also receive subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250μg/m2 twice per week) will given subcutaneously to start 3 days before the 1st armed ATC infusion and ending 7 days after the last dose of armed ATC.
干预措施: therapeutic autologous lymphocytes (Biological)
Aldesleukin, Sargramostim & therapeutic autologous lymphocytes
Peripheral blood mononuclear cells (PBMC) for the generation of ATC will be collected using 1 or 2 phereses to obtain 8-20 × 109 PBMC for T cell expansion. The PBMC will be activated with OKT3 and expanded in IL-2 to generate from 20-320 ×109 ATC during a maximum of 14 days of culture. Three patients will be treated at each dose level. The dose levels for each infusion are: 5, 10, 20, and 40 billion. Each patient will receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encounter toxicities related to armed ATC, the dose and administration will be modified as delineated per the protocol. The patients will also receive subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250μg/m2 twice per week) will given subcutaneously to start 3 days before the 1st armed ATC infusion and ending 7 days after the last dose of armed ATC.
干预措施: Sargramostim (Biological)
Aldesleukin, Sargramostim & therapeutic autologous lymphocytes
Peripheral blood mononuclear cells (PBMC) for the generation of ATC will be collected using 1 or 2 phereses to obtain 8-20 × 109 PBMC for T cell expansion. The PBMC will be activated with OKT3 and expanded in IL-2 to generate from 20-320 ×109 ATC during a maximum of 14 days of culture. Three patients will be treated at each dose level. The dose levels for each infusion are: 5, 10, 20, and 40 billion. Each patient will receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encounter toxicities related to armed ATC, the dose and administration will be modified as delineated per the protocol. The patients will also receive subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250μg/m2 twice per week) will given subcutaneously to start 3 days before the 1st armed ATC infusion and ending 7 days after the last dose of armed ATC.
干预措施: Aldesleukin (Biological)
结局指标
主要结局
Maximum tolerated dose
时间窗: The dose at which dose-limiting toxicity occurs is defined as that dose at which 2 or more of 6 patients at that dose level have their infusions stopped due to toxicities or receive less than 80% of the planned dose.
Toxicity profile
时间窗: Months 1, 2, 5 and 11, then every 6 months
Clinical responses
时间窗: Months: 1, 2, 5 and 11, then every 6 months
Overall survival and progression-free survival
时间窗: The interval from the beginning of immunotherapy to the time of death or for progression free survival it is defined as the interval from the beginning of immunotherapy to progression
次要结局
- Immune changes(1 (+ 7 days), 2 (+ 7 days), 5 months (+ 7 days), then every 6months (+ 7 days) (immune evaluations will also be performed after the 4th and 8th infusion of Her2Bi armed ATC and within 1week of the completion of HER2Bi armed ATC))
研究者
Lawrence Lum
Principal Investigator
Barbara Ann Karmanos Cancer Institute