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.
調査の概要
詳細な説明
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.
研究の種類
入学
段階
- フェーズ 1
連絡先と場所
研究場所
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Washington
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Seattle、Washington、アメリカ、98109
- Fred Hutchinson Cancer Research Center
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Seattle、Washington、アメリカ、98122
- University of Washington (UW)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
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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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二次結果の測定
結果測定 |
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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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協力者と研究者
捜査官
- 主任研究者：Stanley Riddell, MD、Fred Hutchinson Cancer Center
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
研究の完了
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
HIV感染症の臨床試験
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University of Alabama at BirminghamMobile County Health Deparment; Alabama Department of Public Health募集HIV | HIV検査 | HIV とケアの関係 | HIV治療アメリカ
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French National Agency for Research on AIDS and...Elizabeth Glaser Pediatric AIDS Foundation完了パートナーの HIV 検査 | カップルの HIV カウンセリング | カップルのコミュニケーション | HIV の発生率カメルーン, ドミニカ共和国, グルジア, インド
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University of Minnesota引きこもったHIV感染症 | HIV/エイズ | HIV | AIDS | エイズ・HIV問題 | エイズと感染症アメリカ
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Africa Health Research InstituteLondon School of Hygiene and Tropical Medicine; University College, London; University of Southampton と他の協力者募集
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ANRS, Emerging Infectious DiseasesHopital Universitaire Robert-Debre; Institut de Recherche pour le Developpement; Centre Pasteur... と他の協力者わからないHIV | HIVに感染していない子供たち | HIVにさらされた子供たちカメルーン
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Erasmus Medical Centerまだ募集していません
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University of Maryland, Baltimore引きこもった
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Hospital Clinic of Barcelona完了
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University of WashingtonNational Institute of Mental Health (NIMH)募集
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Helios SaludViiV Healthcareわからない
アルデスロイキンの臨床試験
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Carman GiacomantonioNova Scotia Health Authority引きこもった
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Groupe Francophone des MyelodysplasiesEpiCept Corporation引きこもった