Vaccine Therapy in Treating Patients With Stage IV Cutaneous Melanoma
Vaccination of Stage IV Cutaneous Melanoma Patients With Mature, Autologous Monocyte-Derived Dendritic Cells Transfected With RNAs Encoding for Mage-3, MelanA, and Survivin Antigens
RATIONALE: Vaccines made from a person's dendritic cells and antigens may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy using autologous dendritic cells with antigens in treating patients who have stage IV cutaneous melanoma.
研究概览
详细说明
OBJECTIVES:
Primary
- Determine the safety and tolerability of vaccination with autologous monocyte-derived dendritic cells (DC) transfected with RNAs encoding Melan-A, MAGE-3, and survivin antigens in patients with stage IV cutaneous melanoma.
- Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
- Determine whether simultaneous loading of DC with keyhole limpet hemocyanin (KLH) significantly enhances induction of the Melan-A, MAGE-3, and survivin antigens in these patients.
Secondary
- Determine clinical antitumor activity (e.g., objective tumor response, time to tumor progression, progression-free interval, and overall survival) in patients treated with this vaccine.
OUTLINE: This is an open-label, nonrandomized study.
- Phase I: Beginning 9-11 days before vaccination, patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are processed for the generation of dendritic cells (DC) to be used for vaccinations. PBMCs are transfected with RNAs encoding for Melan-A, MAGE-3, and survivin antigens. DC are pulsed with keyhole limpet hemocyanin (KLH) for some patients.
Patients receive antigen-pulsed (with or without KLH) DC vaccination subcutaneously (SC) on days 1, 15, 43, and 71 in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may proceed to the phase II portion of the study.
- Phase II: Patients undergo leukapheresis as in phase I on days 102, 354, and 690. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 127, 185, 269, 356, 521, and 692.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Erlangen、德国、D-91052
- Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
Histologically confirmed cutaneous* melanoma
- Stage IV
- Incurable by surgical resection
- Progressive disease after at least 1 standard chemotherapy or chemoimmunotherapy regimen (e.g., dacarbazine or cisplatin monotherapy)
- Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or noninvasive radiological procedures
No active CNS metastases by CT scan or MRI
- Previously treated (e.g., excision of a single metastasis) CNS metastases are allowed provided there are no signs of active CNS metastases NOTE: *Metastatic melanoma with unidentified primary tumor allowed provided an ocular melanoma can be definitely excluded and origin from the skin is likely
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- At least 4 months
Hematopoietic
- WBC greater than 2,500/mm^3
- Neutrophil count greater than 1,000/mm^3
- Lymphocyte count greater than 700/mm^3
- Platelet count greater than 75,000/mm^3
- Hemoglobin greater than 9 g/dL
- No bleeding disorder
Hepatic
- Bilirubin less than 2.0 mg/dL
- No evidence of hepatitis B or C infection
Renal
- Creatinine less than 2.5 mg/dL
Cardiovascular
- No clinically significant heart disease
Pulmonary
- No respiratory disease
Immunologic
- HIV-1 and HIV-2 negative
- HTLV-1 negative
- No active systemic infection
- No immunodeficiency disease
No active autoimmune disease (e.g., lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, or inflammatory bowel disease)
- Vitiligo allowed
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 weeks after study participation
- Stable medical condition
- No other major serious illness
- No contraindication to leukapheresis
- No organic brain syndrome or significant psychiatric abnormality that would preclude study participation or follow-up
- No other active malignant neoplasm
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior immunotherapy
- No other concurrent immunotherapy during and for 2 weeks after study participation
Chemotherapy
- More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
- No concurrent chemotherapy during and for 2 weeks after study participation
Endocrine therapy
- No concurrent corticosteroids during and for 2 weeks after study participation
Radiotherapy
- More than 2 weeks since prior radiotherapy
- No prior radiotherapy to the spleen
- Concurrent palliative radiotherapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed
Surgery
- Recovered from prior surgery
- No prior splenectomy
- No prior organ allografts
Concurrent surgical therapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed
- Selected accessible metastases may be removed for tumor infiltrating lymphocyte assay or other immunomonitoring investigations (e.g., expression of tumor antigens and HLA molecules)
Other
- No other concurrent investigational drug or paramedical substance during and for 2 weeks after study participation
- No concurrent participation in another clinical trial
- Concurrent palliative medication allowed (e.g., acetaminophen, indomethacin, or opiates)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Safety and tolerability at every visit
大体时间:3 months
|
3 months
|
Overall survival as assessed by clinical staging (CT scan, positron emission tomography [PET]) every 3 months
大体时间:3 months
|
3 months
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Time to progression as assessed by clinical staging (CT scan, PET) every 3 months
大体时间:3 months
|
3 months
|
Objective tumor response as assessed by clinical staging (CT scan, PET) every 3 months
大体时间:3 months
|
3 months
|
Duration of response as assessed by clinical staging (CT scan, PET) every 3 months
大体时间:3 months
|
3 months
|
Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit
大体时间:3 months
|
3 months
|
合作者和调查者
调查人员
- 首席研究员:Gerold Schuler、Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- ERLANGEN-DERMA-ER-DC-06
- CDR0000343699 (注册表标识符:PDQ (Physician Data Query))
- EU-20317
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