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Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma

A Randomized Phase II Study of IL-2 With or Without an Allogeneic Large Multivalent Immunogen (LMI) Vaccine for the Treatment of Stage IV Melanoma

RATIONALE: Aldesleukin may stimulate the white blood cells to kill tumor cells. Vaccines may help the body build an effective immune response to kill tumor cells. Giving aldesleukin together with vaccine therapy may kill more tumor cells. It is not yet known whether aldesleukin is more effective with or without vaccine therapy in treating melanoma.

PURPOSE: This randomized phase II trial is studying how well aldesleukin works when given with or without vaccine therapy in treating patients with stage IV melanoma.

調査の概要

詳細な説明

OBJECTIVES:

Primary

  • To compare the progression-free survival of patients with stage IV melanoma treated with aldesleukin with vs without allogeneic large multivalent immunogen melanoma vaccine LP2307.

Secondary

  • To compare the clinical response in patients treated with these regimens.
  • To compare the 1- and 2-year survival rates in patients treated with these regimens.
  • To determine whether an immune response is generated after vaccination in these patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive allogeneic large multivalent immunogen melanoma vaccine LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II (control): Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on arm I.

Patients undergo blood sample collection periodically for correlative laboratory studies. Samples are analyzed for immune responses to keyhole limpet hemocyanin and tetanus toxoid (control antigens) by ELISA assay; IFN-γ production by CD8 T cells in response to melanoma-derived peptides by ELISpot assay; delayed-type hypersensitivity response to vaccination; and frequency of peripheral blood lymphocytes, including T cells, B cells, NK cells, and monocytes, by flow cytometry.

  • Arm III Crossover: Patients who have progressive disease on Arm II will be offered crossover to Arm I provided they continue to meet all study criteria.

After completion of study treatment, patients are followed every 2 months for 1 year, every 3 months until disease progression, and then periodically thereafter.

研究の種類

介入

入学 (実際)

21

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

    • Minnesota
      • Minneapolis、Minnesota、アメリカ、55455
        • Masonic Cancer Center, University of Minnesota

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  • Stage IV melanoma.
  • Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed if at least 4 weeks since last treatment. Patient must recover from the acute toxic effects of the treatment prior to study enrollment.
  • Disease status must be that of measurable or nonmeasurable disease as defined by Solid Tumor Response Criteria (RECIST)
  • Karnofsky performance status >70% (Eastern Cooperative Oncology Group 0-1)
  • Age 18 years or older
  • Adequate organ function within 14 days of study enrollment including the following:

    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 10^9/L, platelets ≥100 x 10^9/L, and hemoglobin ≥ 10 g/dL
    • Hepatic: bilirubin < 3 times the upper limit of normal (× ULN), aspartate transaminase (AST) < 3 × ULN
    • Renal: creatinine ≤ 2.0
  • Must share at least one class I HLA allele with the HLA-type SK23-CD80+ cell (class I alleles (A1, A2, B7, B8, C7))
  • Meets eligibility criteria for and agrees to enroll in "MT1999- 06: Vaccination with Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune Responses" (IRB # 9904M01581, CPRC #2002LS032)
  • Women of childbearing potential and men whose partners are of childbearing potential are required to use an effective method of contraception (ie, a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after the last dose of study drug.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion criteria:

  • History of brain metastases or positive brain scan at on-study
  • Immunosuppressive therapy i.e., prednisone or organ transplant patients, however topical or inhalational steroids are allowed.
  • Autoimmune diseases requiring immunosuppressive therapy.
  • History of symptomatic pulmonary disease will have pulmonary function tests (PFTs) performed. Patients with symptoms of dyspnea or rales, wheezes or rhonchi on physical exam will undergo PFTs. Those with FEV1 <50% of predicted or corrected DLCO <50% are not eligible.
  • Patients with cardiac disease such as recent myocardial infarction (< 3 months prior), unstable angina, or heart failure requiring medical intervention will undergo cardiac evaluation. Cardiac testing may include ECG, MUGA or echocardiogram, and/or thallium stress test as indicated to evaluate cardiac risks. Those patients with exercise-induced ischemia or an ejection fraction by MUGA or echocardiogram < 40% are not eligible.
  • Due to the origin of the KLH protein, patients with a history of seafood allergy are excluded from receiving KLH.
  • Hypersensitivity to any component of the vaccine, including Thimerosal, a mercury derivative, is a contraindication (taken from tetanus toxoid package insert).
  • The occurrence of any type of neurologic symptoms to tetanus vaccine in the past is a contraindication to further use (taken from tetanus toxoid package insert).
  • Subjects who have had tetanus toxoid within the last 7 years will not receive the tetanus vaccine component of this
  • Pregnant (positive pregnancy test) or lactating women. Use of LMI vaccine during pregnancy is not approved for use by the FDA during pregnancy. IL-2 is pregnancy category C - risk in pregnancy cannot be ruled out.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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:ランダム化
  • 介入モデル:クロスオーバー割り当て
  • 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
実験的:Arm I - LMI + aldesleukin
Patients receive allogeneic large multivalent immunogen vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
他の名前:
  • プロロイキン
  • IL-2
  • インターロイキン-2
Allogeneic tumor cell membrane-coated large multivalent immunogen (LMI [1 x 10^7, 5-μm silica spheres]) will be given as an intradermal injection every 4 weeks for up to 12 injections. Each vaccine dose will be 0.2 ml.
他の名前:
  • LMI vaccine
アクティブコンパレータ:Arm II (control) - aldesleukin
Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on arm I.
IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
他の名前:
  • プロロイキン
  • IL-2
  • インターロイキン-2
実験的:Arm III - Crossover Patients

Patients who have progressive disease on Arm II were be offered crossover to Arm I provided they continued to meet all study criteria.

Patients receive allogeneic large multivalent immunogen vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity

IL-2 Alone - administer 10 x 10^6 International Units subcutaneously (SQ) will be given on day 1 and day 2 every 4 weeks until disease progression or for a maximum of 12 treatment cycles.
他の名前:
  • プロロイキン
  • IL-2
  • インターロイキン-2
Allogeneic tumor cell membrane-coated large multivalent immunogen (LMI [1 x 10^7, 5-μm silica spheres]) will be given as an intradermal injection every 4 weeks for up to 12 injections. Each vaccine dose will be 0.2 ml.
他の名前:
  • LMI vaccine

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
Median Time of Progression-free Survival
時間枠:From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.
Progression free survival (PFS) was measured in months from date of randomization to date of disease progression, or date of death. For patients who died without tumor progression, PFS assumes their deaths are randomly related to tumor progression. Therefore, PFS includes deaths if they came first.
From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.

二次結果の測定

結果測定
メジャーの説明
時間枠
Clinical Response of Lesion(s)
時間枠:Month 2 through Month 12
Beginning at 2 months Through End of Treatment: To determine clinical response of each treatment group - Best Clinical response will be determined using Solid Tumor Response Criteria (RECIST). Complete Response (CR) = complete disappearance of all target lesions. Partial Response (PR) = At least a 30% decrease in sum of longest diameters of target lesions. Progressive Disease (PD) = At least a 20% increase in sum of longest diameters of target lesions. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR or PD.
Month 2 through Month 12
Overall Survival at 2 Years
時間枠:2 Years
Two year survival (alive at 2 years from randomization) rate of each treatment group.
2 Years
Overall Survival at 1 Year
時間枠:1 Year
One year survival (alive at 1 year from randomization) rate of each treatment group.
1 Year
Immune Response
時間枠:48 hours After Study Medication
Immune responses is be assessed by Delayed Type Hypersensitive (DTH) responses to LMI, IFN-γ production by CD8 T cells using the ELISPOT assay, and CD8 T cell binding to HLA-A2 multimers complexed with melanoma-derived peptides (pentamer analysis). DTH reactions are determined at 48 hours by measuring the largest diameter and right angle diameter of the area of induration and calculating the mean. DTH responses are recorded as present or absent but cannot be used as a quantitative measure of immune activation.
48 hours After Study Medication

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2008年6月1日

一次修了 (実際)

2011年6月1日

研究の完了 (実際)

2011年6月1日

試験登録日

最初に提出

2008年7月31日

QC基準を満たした最初の提出物

2008年7月31日

最初の投稿 (見積もり)

2008年8月1日

学習記録の更新

投稿された最後の更新 (実際)

2017年12月28日

QC基準を満たした最後の更新が送信されました

2017年12月3日

最終確認日

2017年12月1日

詳しくは

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医薬品およびデバイス情報、研究文書

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米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

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