Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma (MARVSmALo)
Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma
調査の概要
詳細な説明
The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.
The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.
The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Kansas
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Fairway、Kansas、アメリカ、66205
- KU Cancer Center
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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:
- Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
- Life expectancy of at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
Laboratory Values
- absolute neutrophil count > 500 microliters (mcL)
- platelet > 50,000 mcL
- serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal (IULN)
- total bilirubin < 3 x IULN
- serum creatinine < 3 x IULN
- Pulse oximetry of > 95% on room air.
- Must have recovered from the toxic effects of all prior chemotherapy
Exclusion Criteria:
- Patients with rapidly progressive disease.
- Patient is currently receiving any investigational drugs
- Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
- Patients must not have tumor in a location where enlargement could cause airway obstruction
- Patient is pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products.
- Currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporin
- Received any tumor vaccines within previous six weeks
- Known hypersensitivity to rat monoclonal antibodies
- History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus, Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).
- Allergy to baker's yeast or other components of the vaccines.
- History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B
- History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a cause other than the vaccine was indicated.
- Melanoma involvement of the central nervous system
- Chemotherapy given within the last 28 days
- Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
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：なし
- 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）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：tvs-CTL Vaccine
Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells.
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autologous, 14g2a.zeta
chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)
|
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
時間枠：4 weeks
|
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
|
4 weeks
|
|
PCR measurement of retroviral construct to measure persistence of infused T-cells
時間枠：4 weeks
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To evaluate how long the infused T-cells remain in the blood stream
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4 weeks
|
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Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
時間枠：4 weeks
|
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
|
4 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
PCR measurement of retroviral construct to measure the expansion of infused T-cells
時間枠：12 months
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To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
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12 months
|
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PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
時間枠：12 months
|
To compare the frequency of tvs-CTL in the peripheral blood, after revaccination, to the frequency noted in the prior study of autologous activated, CAR-transduced T-cells infused in patients with relapsed, refractory Stage IV melanoma
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12 months
|
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Imaging studies to measure tumor response
時間枠：10 weeks
|
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.
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10 weeks
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Gary Doolittle, MD、University of Kansas Medical Center
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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 (実際)
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
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