Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.
研究概览
详细说明
OBJECTIVES:
Primary
- Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma.
Secondary
- Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay.
- Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
- Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
- Correlate treatment-associated changes in immune response with clinical outcome.
OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines.
- Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor [TNF] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217[210M] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin [KLH; first course] or pan-DR epitope [PADRE] [second course]) every 6 hours on days 1-4 of weeks 1 and 6.
- Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6.
Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 10 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity.
In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity.
Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements.
After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Pennsylvania
-
Pittsburgh、Pennsylvania、美国、15232
- UPMC Cancer Centers
-
Pittsburgh、Pennsylvania、美国、15213
- UPMC Cancer Center at Magee-Womens Hospital
-
-
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:
Pathologically confirmed stage III or IVA (M1a) melanoma
- Recurrent and inoperable disease
- Any tumor thickness and any number of lymph nodes involved
- Asymptomatic cutaneous and nodal disease allowed
- Asymptomatic pulmonary metastatic disease (stage IVB, M1b) allowed
- No advanced symptomatic visceral disease, including any symptomatic visceral organ involvement, or disease associated with increased serum lactic dehydrogenase > 2.5 times upper limit of normal (stage IVC, M1c)
- Standard curative or palliative measures do not exist or are no longer effective
Sufficient numbers of monocytes (≥ 20 x 10^6) must be obtained for the preparation of the vaccine
- If an insufficient number of cells is obtained on first venipuncture, a second venipuncture may be performed (not exceeding 550 mL of blood within 8 weeks)
No brain metastases by contrast-enhanced CT scan or MRI
- Prior brain metastases allowed provided they were successfully treated and patient has been asymptomatic for ≥ 3 months
- HLA-A2 positive
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 6 months
- Granulocyte count ≥ 1,500/mm³
- Lymphocyte count ≥ 500/mm³
- Platelet count > 70,000/mm³ (for venipuncture/pheresis procedure)
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Gamma-glutamyl transferase ≤ 2.5 times ULN
- Lactic dehydrogenase ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Bilirubin ≤ 1.5 times ULN
- No active infection
- No sensitivity to drugs that provide local anesthesia
- No pain uncontrolled by oral analgesics, including opiates and opiate analogs
- No active autoimmune disease
- No HIV, hepatitis B, or hepatitis C positivity
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Negative pregnancy test
- No other malignancy except for nonmelanoma skin cancers or carcinoma in situ of the cervix, or other malignancy for which the patient has been continuously disease-free for ≥ 2 years
PRIOR CONCURRENT THERAPY:
- Recovered from prior surgery
- No radiotherapy, chemotherapy, or immunotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
- No antibiotics within the past 7 days
No systemic immunosuppressive agents, including steroids, within the past 4 weeks
- Concurrent maintenance steroids for adrenal insufficiency allowed
- No other concurrent anticancer investigational or commercial agents or therapies
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：peptide-pulsed type-1-polarized dendritic cells
intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1)
|
|
|
实验性的：peptide-pulsed mature non-polarized dendritic cells (cDCs)
intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs)
|
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
大体时间：7 years
|
7 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Assess immune responses to each dendritic cell vaccine outcome
大体时间：7
|
i. Peripheral blood CD8+ and CD4+ T cell responses against HLA-presented melanoma epitopes, and (in patients with available tumor tissue) against autologous tumor cells, and using IFNγ-, and IL-5- ELISPOT assays. CD8+ T cell responses (IFNγ ELISPOT) will be used as a secondary readout: the sum of the specific ELISPOT counts obtained (at week 8) with each of the individual HLA-A2-restricted peptides (less the respective counts obtained before the treatment), will be considered as a primary indication of the vaccine effectiveness. ii. Delayed type hypersensitivity (DTH) response to the mix of the melanoma-related peptides, injected intradermally in vivo, and DTH to autologous tumor lysates, in all cases when autologous tumor tissue is available. iii. Delayed type hypersensitivity (DTH) responses to KLH and PADRE injected intradermally in vivo. |
7
|
合作者和调查者
调查人员
- 首席研究员：Ahmad A. Tarhini, MD, MS、University of Pittsburgh
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 (实际的)
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
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
polarized dendritic cells的临床试验
-
Universidad de la SabanaFundación Neumologica Colombiana; Stem Medicina Regenerativa; Innocell SAS可用的
-
The First Affiliated Hospital of Soochow UniversityFundamenta Therapeutics, Ltd.招聘中
-
Yan JinXijing Hospital; Tang-Du Hospital未知