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Active Immunotherapy Of Metastatic Renal Cell Carcinoma Using Autologous Dendritic Cells Transfected With Autologous Total Tumor RNA

The feasibility and dose-limiting toxicity of administering escalating doses of dendritic cells transfected with autologous renal cell carcinoma RNA DC(DCRCC-RNA) will be defined. As a secondary endpoint, the ability of DCRCC-RNA to induce tumor-specific immune responses will be evaluated. Finally, the anti-tumor effects measured by clinical response criteria, their duration and overall survival (calculated at 2-year follow-up) will be determined in each patient receiving dendritic cell therapy.

Background: Prognosis in metastatic renal cell carcinoma is poor with a median survival of less than one year. Although renal cell carcinoma has shown some response to immunotherapy, the results of systemic administration of biologic response modifiers in disseminated renal cell carcinoma have been poor. Growing evidence suggests that active immunotherapy, particularly dendritic cells (DC) based vaccines, may prove to be a viable and clinically effective therapeutic option for patients with advanced or metastatic renal cell carcinoma.

調査の概要

状態

わからない

詳細な説明

Methods: This study will enroll patients with renal cell carcinoma Stage III (T3 N1 M0) or Stage IV (T4 N0 N1 M0 - any T N2 M0 - any T any N M1) after nephrectomy. Peripheral blood mononuclear cells collected through leukapheresis are processed for DC generation. Mononuclear cells are separated and cultured for 7 days in GM-CSF and IL-4. Harvested DC will be pulsed with renal tumor RNA harvested during nephrectomy. An aliquot of these cells will be tested for appropriate phenotype fungal and bacterial sterility as well as for endotoxin content prior to lot release. Renal tumor RNA transfected DC will be stored cryopreserved until administration.

The first 3 patients will be enrolled at a low dose and monitored for dose limiting toxicities. If no dose limiting toxicities are seen, the next 3 patients will be enrolled at the medium dose. If no dose limiting toxicities are seen in the medium dose, 6 additional patients will be enrolled on the high dose and will be evaluated for dose limiting toxicities. If in preparation of the vaccine insufficient RNA or dendritic cells are available to perform the required three injections at the assigned dose level or if the patient is withdrawn from the study the treatment position will remain open, i.e., no dose fractions will be given. Patients in whom only the minimum number of DCRCC-RNA can be produced to deliver one I.V. and one I.D. injection will be able to receive the vaccine, even if he or she is assigned to a higher dose level, but will be replaced in order to assess toxicity.

Data Analysis 1. To determine the short and long term toxicities associated with administration of DCRCC-RNA in patients with metastatic RCC. 2. To determine feasibility of DC vaccine generation according to the proportion of patients for whom sufficient cells are generated to provide treatment. 3. To determine the cellular immune response to administration of DCRCC-RNA. 4. To measure the clinical responses mediated by administration of DCRCC-RNA.

研究の種類

介入

段階

  • フェーズ 1

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

    • North Carolina
      • Durham、North Carolina、アメリカ、27710
        • Duke University Medical Center

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:

  • Patients with metastatic RCC following resection of the primary renal tumor (Pathologic diagnosis and staging of the disease will be completed at time of surgery).
  • Patients must have a performance status of 0 or 1 according the Eastern Cooperative Oncology Group (ECOG) criteria and must have an estimated life expectancy of 6 months and more.
  • Patients must not have undergone any major surgery during the past 6 weeks. In addition no chemotherapeutic agents, (standard or experimental) radiation therapy, (local therapy or palliative treatment for painful bony metastases) or immunotherapy (i.e. IL-2, interferon-alpha, ALT therapy) can be administered 6 weeks prior to enrollment. Patients must have recovered from all acute toxicities from prior treatment.
  • Adequate hematologic function with: WBC 3000 mm3, hemoglobin 9 mg/dl, platelets 100,000/mm3
  • Patients may be transfused to meet the eligibility criteria.
  • Adequate renal and hepatic function with: serum creatinine < 2.5 mg/dl, bilirubin < 2.0 mg/dl
  • Adequate coagulation parameters with: Partial thromboplastin time < 1.5 x control
  • Ability to understand and provide signed inform consent that fulfills Institutional Review Board guidelines
  • Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol.

Exclusion Criteria:

  • Women who are pregnant and nursing women are excluded.
  • Patients after radical nephrectomy are excluded since no tumor tissue can be retrieved and no vaccine generated.
  • Patients with either previously irradiated or new CNS (central nervous system) metastases as determined by enhanced cranial CT or MRI prior to enrollment.
  • Patients with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
  • Patients with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
  • Medical or psychological impediment to probable compliance with the protocol.
  • Patients with prior history of another malignancy within the last 5 years (excluding basal cell carcinoma, carcinoma in situ of the cervix, non-melanoma skin cancer, or controlled superficial bladder cancer).
  • Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot), viral hepatitis (as determined by HBsAg and Hepatitis C serology) and surgical site infection following nephrectomy. Any postoperative complication rendering experimental therapy unduly hazardous i.e. deep venous thrombosis (DVT) or pulmonary embolism will exclude eligibility from study.
  • Patients on steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment.
  • Patients with serum calcium >12 mg/dl or symptomatic hypercalcemia. Documented active treatment for hypercalcemia is allowed.
  • Patients with inadequate peripheral vein access to perform leukapheresis.

研究計画

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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

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。

協力者

捜査官

  • 主任研究者:Johannes Vieweg, M.D.

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。

試験登録日

最初に提出

2000年11月3日

QC基準を満たした最初の提出物

2000年11月3日

最初の投稿 (見積もり)

2000年11月6日

学習記録の更新

投稿された最後の更新 (見積もり)

2005年6月24日

QC基準を満たした最後の更新が送信されました

2005年6月23日

最終確認日

2001年11月1日

詳しくは

本研究に関する用語

その他の研究ID番号

  • NCRR-M01RR00030-0153
  • M01RR000030 (米国 NIH グラント/契約)

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。

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