Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Primary CNS Lymphoma
Intensive Chemotherapy And Immunotherapy In Patients With Newly Diagnosed Primary CNS Lymphoma
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well rituximab given with combination chemotherapy works in treating patients with newly diagnosed primary CNS lymphoma.
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
Primary
- Determine the complete response rate after remission induction therapy with the combination of high-dose methotrexate (HDMTX), temozolomide, and rituximab at 4 months.
Secondary
- Determine the safety and feasibility of consolidation therapy comprising cytarabine and etoposide administered after induction therapy in these patients.
- Determine the percentage of patients who achieve durable (complete and partial) remission when treated with this regimen.
- Determine relapse-free survival after complete response in patients treated with this regimen.
- Correlate molecular markers with outcome in patients treated with this regimen.
- Determine the effects of this regimen on neurological function in these patients.
OUTLINE: This is a multicenter study.
Induction Chemotherapy: All induction therapy courses repeat every 28 days.
- Courses 1-3: Patients receive high-dose methotrexate IV over 4 hours on days 1 and 15, leucovorin calcium IV or orally every 6 hours beginning on days 2 and 16 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. Patients also receive rituximab* IV on days 3, 10, 17, and 24 of course 1 and days 3 and 10 of course 2 (total of 6 doses).
NOTE: *Patients diagnosed with T-cell primary CNS lymphoma do not receive rituximab.
Course 4: Patients receive oral temozolomide on days 7-11, high-dose methotrexate IV over 4 hours on day 15, and leucovorin calcium IV or orally every 6 hours beginning on day 16 and continuing until blood levels of methotrexate are in a safe range. Patients achieving a complete response or a complete response unconfirmed proceed to consolidation therapy.
- Consolidation therapy I (course 5): Beginning 4 weeks after the start of course 4, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11.
- Consolidation therapy II (course 6): Beginning 3-5 weeks after the start of course 5, patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 12 hours twice daily on days 1-4 and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.
Treatment continues in the absence of disease progression.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 27-45 patients will be accrued for this study within 2-3 years.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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California
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San Francisco、California、アメリカ、94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Delaware
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Lewes、Delaware、アメリカ、19958
- Tunnell Cancer Center at Beebe Medical Center
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Newark、Delaware、アメリカ、19713
- CCOP - Christiana Care Health Services
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Illinois
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Chicago、Illinois、アメリカ、60637-1470
- University of Chicago Cancer Research Center
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Indiana
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Fort Wayne、Indiana、アメリカ、46845
- Fort Wayne Medical Oncology and Hematology
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Iowa
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Bettendorf、Iowa、アメリカ、52722
- Hematology Oncology Associates of the Quad Cities
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Kansas
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Overland Park、Kansas、アメリカ、66209
- Menorah Medical Center
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Overland Park、Kansas、アメリカ、66213
- Saint Luke's Hospital - South
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Shawnee Mission、Kansas、アメリカ、66204
- Shawnee Mission Medical Center
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Maryland
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Elkton MD、Maryland、アメリカ、21921
- Union Hospital Cancer Program at Union Hospital
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
- Masonic Cancer Center at University of Minnesota
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Missouri
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Kansas City、Missouri、アメリカ、64131
- CCOP - Kansas City
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Kansas City、Missouri、アメリカ、64116
- North Kansas City Hospital
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Kansas City、Missouri、アメリカ、64132
- Research Medical Center
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Kansas City、Missouri、アメリカ、64108
- Truman Medical Center - Hospital Hill
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Kansas City、Missouri、アメリカ、64111
- Saint Luke's Cancer Institute at Saint Luke's Hospital
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Kansas City、Missouri、アメリカ、64114
- St. Joseph Medical Center
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Kansas City、Missouri、アメリカ、64116
- Parvin Radiation Oncology
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Lee's Summit、Missouri、アメリカ、64086
- Saint Luke's East - Lee's Summit
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Liberty、Missouri、アメリカ、64068
- Liberty Hospital
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Saint Joseph、Missouri、アメリカ、64506
- Heartland Regional Medical Center
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New Jersey
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Voorhees、New Jersey、アメリカ、08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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Stony Brook、New York、アメリカ、11794-9446
- Stony Brook University Cancer Center
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Syracuse、New York、アメリカ、13210
- SUNY Upstate Medical University Hospital
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Ohio
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Columbus、Ohio、アメリカ、43210-1240
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Rhode Island
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Providence、Rhode Island、アメリカ、02906
- Miriam Hospital
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Providence、Rhode Island、アメリカ、02903
- Rhode Island Hospital Comprehensive Cancer Center
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Vermont
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Berlin、Vermont、アメリカ、05602
- Mountainview Medical
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Burlington、Vermont、アメリカ、05401
- Fletcher Allen Health Care - University Health Center Campus
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Virginia
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Danville、Virginia、アメリカ、24541
- Danville Regional Medical Center
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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:
Histologically confirmed newly diagnosed primary CNS lymphoma confirmed by 1 of the following methods:
- Brain biopsy or resection
Cerebrospinal fluid (CSF) cytology
- Positive CSF cytology with or without measurable intracranial disease
No evidence of systemic non-Hodgkin's lymphoma
- CT scan or MRI of the chest, abdomen, and pelvis AND bilateral bone marrow biopsy or unilateral biopsy with a 2cm core biopsy specimen that is negative for extracerebral source of lymphoma
- Measurable contrast-enhancing disease by MRI of the brain and spine (plus gadolinium) unless CSF cytology positive
- No evidence of pleural effusions or ascites
PATIENT CHARACTERISTICS:
Age
- Any age
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
Hepatic
- ALT and AST ≤ 2 times upper limit of normal
- Bilirubin ≤ 2 mg/dL
Renal
- Creatinine clearance ≥ 50 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months after study participation
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Concurrent steroids for the management of symptoms related to lymphoma allowed
Radiotherapy
- No concurrent palliative radiotherapy
Surgery
- Not specified
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 |
|---|---|
|
実験的：Intensive Combination Chemo & Immunotherapy
Induction Cycles 1-3: Methotrexate 8gm/m^2 days 1 & 15; Leucovorin 100 mg/m^2 days 2 & 16; Rituximab 375 mg/m^2 days 3, 10, 17 & 24 of cycle 1, days 3 & 10 of cycle 2; Temozolomide 150 mg/m^2/day PO days 7-11 Induction Cycle 4: Temozolomide 150 mg/m^2/day PO days 7-11; Methotrexate 8gm/m^2 day 15; Leucovorin 100 mg/m^2 day 16 Consolidation Cycle 5: Methotrexate 8gm/m^2 days 1; Leucovorin 100 mg/m^2 days 2; Temozolomide 150 mg/m^2/day PO days 7-11 Consolidation Cycle 6: Cytarabine 2 g/m^2 (x 8 doses) days 1-4; Etoposide 5 mg/kg (x 8 doses) days 1-4; G-CSF 5 mcg/kg/day or GM-CSF 250 mcg/m^2/day starting day 14 until ANC recovers (>= 500 for 2 consecutive days or >= 1500 for one day) |
5 mcg/kg subQ injection daily Day 14 until ANC > or = 500 uL for 2 days or 1500 uL for 1 day (Cycle 6)
他の名前：
375 mg/sq m IV infusion (max rate of 400 mg/hr) on Days 3, 10, 17, & 24 of Cycle 1 nad Days 3 & 10 of Cycle 2
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
100 mg/sq m IV infusion q 6 hrs starting 24 hrs after ea MTX dose until serum MTX < or = 0.05uM Cycles 1-5.
8 g/sq m IV infusion over 4 hrs Days 1 & 15 Cycles 1, 2, & 3; Day 15 Cycle 4 and Day 1 Cycle 5.
150 mg/sq m PO Days 7-11 Cycles 1-5.
|
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 |
|---|---|---|
|
Complete Response Rate After Remission Induction
時間枠：4 months
|
Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma.
Complete response requires disappearance of all evidence of disease.
|
4 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
4 Year Progression Free Rate
時間枠：4 years
|
Percentage of patients who were progression free at 4 years. The 4-year progression free rate was estimated using the Kaplan Meier method. Relapse was assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Progression required a 25% increase of previous area of gadolinium enhancement, appearance of new areas of T1 gadolinium enhancement or new appearance of malignant cells in the spinal fluid or new tumor appearance in other sites of the body |
4 years
|
|
Change From Baseline in Mini-Mental Status Evaluation at 4 Months
時間枠：Baseline & month 4
|
Neurologic functioning will be assessed using the Mini-Mental Status Evaluation (MMSE), a standardized, bedside tool for evaluation of higher mental function.
This assessment is based on a 30-point scale (0-30) with higher scores associated with better performance.
|
Baseline & month 4
|
|
4 Year Overall Survival Rate
時間枠：4 years
|
Percentage of patients who were alive at 4 years.
The 4-year survival rate was estimated using the Kaplan Meier method.
|
4 years
|
協力者と研究者
捜査官
- スタディチェア：James Rubenstein, MD, PhD、University of California, San Francisco
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
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 (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
- 免疫系疾患
- 組織型別の新生物
- 新生物
- リンパ増殖性疾患
- リンパ疾患
- 免疫増殖性疾患
- リンパ腫
- 薬の生理作用
- 薬理作用の分子機構
- 抗感染剤
- 抗ウイルス剤
- 核酸合成阻害剤
- 酵素阻害剤
- 抗リウマチ剤
- 代謝拮抗薬、抗腫瘍薬
- 代謝拮抗剤
- 抗悪性腫瘍薬
- 免疫抑制剤
- 免疫学的要因
- 保護剤
- 抗悪性腫瘍薬、アルキル化
- アルキル化剤
- 抗悪性腫瘍剤、ファイトジェニック
- トポイソメラーゼ II 阻害剤
- トポイソメラーゼ阻害剤
- 抗悪性腫瘍剤、免疫
- 皮膚科用薬
- 微量栄養素
- ビタミン
- カルシウム調節ホルモンおよびエージェント
- 生殖制御剤
- 解毒剤
- ビタミンB複合体
- 妊娠中絶薬、非ステロイド系
- 中絶エージェント
- 葉酸拮抗薬
- エトポシド
- テモゾロミド
- リツキシマブ
- ロイコボリン
- カルシウム
- レボルコボリン
- シタラビン
- メトトレキサート
その他の研究ID番号
- CALGB-50202
- U10CA031946 (米国 NIH グラント/契約)
- CDR0000398106 (レジストリ識別子：NCI Physician Data Query)
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。