Safety and Effectiveness of Immunotherapy With Autologous HIV-Specific CD8 Cells in HIV Infected Adults
Safety and Antiviral Efficacy of Cellular Adoptive Immunotherapy With Autologous CD8+ HIV-Specific Cytotoxic T Cells Combined With Interleukin-2 For HIV Seropositive Individuals
Effective, suppressive treatment for HIV infected patients can be a major challenge because HIV progressively destroys their immune systems. CD8 cells isolated from a patient's blood and grown in large numbers in the laboratory may increase a patient's immune system response to HIV. The purpose of this study is to determine if CD8 cells will provide effective antiviral activity against HIV when transplanted back in large numbers into HIV infected patients.
Study hypothesis: There are specific cells in the immune system that recognize and can kill HIV-infected cells.
研究概览
详细说明
The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells. However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo. Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of antiviral activity without severe toxicity.
This study will last 18 months. CD8 cells will be isolated from the blood of HIV infected patients; the cells will be allowed to multiply in the laboratory, and patients will receive back their CD8 cells. Patients will receive up to 3 infusions of self CD8 cells. On Day 0, patients will receive their first infusion of CD8 cells. On Day 7, patients will receive their second infusion of CD8 cells; this infusion will be followed by 14 days of aldesleukin administered daily by injection under the skin. Patients with less than a Grade 2 toxicity will receive a third infusion of CD8 cells; this infusion will be followed by 21 days of aldesleukin.
研究类型
注册
阶段
- 阶段1
联系人和位置
学习地点
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Washington
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Seattle、Washington、美国、98109
- Fred Hutchinson Cancer Research Center
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Seattle、Washington、美国、98122
- University of Washington (UW)
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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
Inclusion Criteria for All Participants:
- HIV infected
- CD4 count greater than 200 cells/mm3 at study entry
- Absolute neutrophil count greater than 1000 cells/mm3
- Willing to take Pneumocystis prophylaxis, if indicated
- Willing to comply with study requirements
- Willing to forgo other experimental therapy during the 26-week study period
- Willing to use acceptable forms of contraception
Inclusion Criteria for Treatment-Experienced Participants:
- Currently receiving treatment with an FDA-approved or expanded access antiretroviral agent (or combinations thereof) at a stable dose for at least 24 weeks prior to study entry
Inclusion Criteria for Treatment-Naive Participants:
- Have not received antiretroviral therapy for 6 months prior to study entry
Exclusion Criteria:
- Treatment with other immunomodulatory therapies (interferon, HIV vaccines, intravenous immunoglobulin), pentoxifylline, cancer chemotherapy, radiation therapy, or other investigational agents
- Past or present infection with mycobacterium avium complex, toxoplasmosis, cryptococcus, or cytomegalovirus (including retinitis)
- Active opportunistic infection at study entry or serious systemic infection requiring chronic maintenance or suppressive therapy
- Lymphoma, symptomatic visceral Kaposi's sarcoma, or any malignancy expected to require systemic therapy
- Serious psychological or emotional disorder that would affect ability to comply with study requirements or that would be exacerbated by protocol participation
- Alcohol or drug use, abuse, or dependence that, in the opinion of the investigator, would interfere with the study
- Estimated life expectancy of less than 4 months
- Abnormal neurocognitive examination
- Significant abnormality on electrocardiogram or chest radiograph
- Inability to generate CD8+ HIV-specific cytotoxic T cell clones
- Previously treated in FHCRC Protocol #827.1
- Pregnancy or breastfeeding
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 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 |
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To determine the safety of administering CD8+ HIV-specific CTL clones followed by subcutaneous IL-2 (Proleukin, Chiron) daily for up to 21 days
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To identify a regimen of IL-2 that will improve the in vivo persistence and function of adoptively transferred CD8+ HIV-specific CTL
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次要结果测量
结果测量 |
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To determine whether the administration of IL-2 prolongs the antiviral activity of transferred CD8+ HIV-specific CTL
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To determine if IL-2 promotes the accumulation of adoptively transferred CD8+ HIV-specific CTL in lymph nodes
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合作者和调查者
调查人员
- 首席研究员:Stanley Riddell, MD、Fred Hutchinson Cancer Center
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
研究完成
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
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.
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