Biological Therapy After Chemotherapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
A Phase I Study To Evaluate The Safety Of Cellular Immunotherapy Using Genetically Modified Autologous Cd20-Specific Cd8+ T Cell Clones For Patients With Relapsed Cd20+ Indolent Lymphomas
RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining biological therapy with chemotherapy may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of biological therapy after chemotherapy in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the safety and toxicity of cellular immunotherapy with autologous CD8+ cytotoxic T-lymphocyte clones after chemotherapy comprising cyclophosphamide, vincristine, and prednisone in patients with relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma.
Secondary
- Determine the duration of in vivo persistence of adoptively transferred CD20-specific CD8+ cytotoxic T-lymphocyte clones in the absence and presence of subcutaneous interleukin-2 in these patients.
- Assess the trafficking of CD8+ cytotoxic T-lymphocyte clones to lymph nodes in these patients treated with this regimen.
- Determine immune response and tumor response in patients treated with this regimen.
OUTLINE: This is an open-label, pilot study.
- Leukapheresis: Patients undergo leukapheresis. Selected CD20-specific CD8+ cells are cultured to expand the cytotoxic T lymphocytes (CTL), which are then cloned.
- Chemotherapy:
Patients receive oral cyclophosphamide and oral prednisone on days 1-5 and vincristine IV on day 1. Courses repeat every 3-4 weeks for a total of 6 courses.
- Immune cell infusion:
Beginning 4 weeks after the last course of chemotherapy (and lymph nodes ≤ 5 cm diameter or ≤ 5,000 circulating CD20+ lymphocytes/mm^3), patients receive autologous CD8+ CTL clones IV over 30 minutes. Courses repeat every 2-5 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. The last 6 patients receive interleukin-2 subcutaneously every 12 hours for 14 days, beginning 2 hours after the last infusion of CD8+ CTL clones.
After course 2 or 3 of immune cells, all patients undergo surgical lymph node biopsy to determine if immune cells are moving to the lymph nodes.
Patients are followed monthly for 1 year and then annually for 2 years.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 4 years.
研究の種類
入学 (予想される)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
California
-
Duarte、California、アメリカ、91010-3000
- City of Hope Comprehensive Cancer Center
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-
Washington
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Seattle、Washington、アメリカ、98195
- University of Washington School of Medicine
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Seattle、Washington、アメリカ、98109-1024
- Fred Hutchinson Cancer Research Center
-
-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
説明
DISEASE CHARACTERISTICS:
Immunohistopathologically documented relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma
Indolent B-cell lymphomas including any of the following subtypes:
- Follicular lymphoma (grade I, II, or III)
- Small lymphocytic lymphoma or chronic lymphocytic leukemia
- Marginal zone lymphoma (splenic, nodal, and extra-nodal)
- Lymphoplasmacytoid lymphoma
- Ineligible for or unwilling to participate in other FHCRC/UWMC protocols
- Serological evidence of prior exposure to Epstein-Barr virus
- Must agree to undergo peripheral blood drawing, bone marrow biopsy, lymph node biopsy, and nuclear medicine imaging
- Must agree to cytoreductive chemotherapy if necessary to reduce lymph nodes to < 5 cm in diameter or circulating B lymphocyte counts to < 5,000/mm^3
- No pulmonary involvement
- No CNS involvement
PATIENT CHARACTERISTICS:
Age:
- Any age
Performance status:
- Not specified
Life expectancy:
- At least 90 days
Hematopoietic:
- Not specified
Hepatic:
- No active hepatitis B infection
Renal:
- Not specified
Other:
- No HIV positivity
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No history of hypersensitivity reactions to murine proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 months since prior rituximab, tositumomab, or ibritumomab
- No prior allogeneic stem cell transplantation
- No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular products)
Chemotherapy:
- At least 2 years since prior fludarabine or cladribine
- At least 4 weeks since prior chemotherapy and recovered
Endocrine therapy:
- No concurrent systemic corticosteroids except to treat toxicity from chemotherapy or cellular immunotherapy
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- At least 4 weeks since prior immunosuppressive therapy and recovered
- No concurrent pentoxifylline
- No other concurrent investigational agents
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
- 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 |
|---|
|
Safety and toxicity by NCI CTC toxicity scale in patients w/ recurr. or refract. CD20+ follicular lymphoma who are not candidates for high dose chemoradiotx and stem cell transplant during each infusion, weekly for 4 wks and then monthly for a yr
|
二次結果の測定
結果測定 |
|---|
|
Duration of in vivo persistence of adoptively transferred CD20-specific CD8+ T cell clones by flow cytometry and quantitative polymerase chain reaction (qPCR) during each infusion, weekly for 4 weeks, and then monthly for a year
|
|
Trafficking of CD8+ CD20-specific T cell clones to lymph nodes by Gamma camera imaging during each infusion, weekly for 4 weeks, and then monthly for a year
|
|
Development of host anti-scFvFc:zeta (and anti-NeoR) immune responses by ELISA and chromium release assays during each infusion, weekly for 4 weeks, and then monthly for a year
|
|
Tumor responses to cyclophosphamide, vincristine, and prednisone (CVP) and to cytotoxic T-lymphocyte (CTL) infusions by Cheson criteria during each infusion, weekly for 4 weeks, and then monthly for a year
|
協力者と研究者
捜査官
- スタディチェア：Oliver W. Press, MD, PhD、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 (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 (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
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 1503.00
- FHCRC-1503.00
- NCI-G01-1921
- CDR0000068494 (レジストリ識別子：PDQ)
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