Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
2018年2月1日 更新者：Radiation Therapy Oncology Group
Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma
RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.
調査の概要
状態
完了
条件
詳細な説明
OBJECTIVES:
- To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma.
- To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.)
- To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10.
- To report progression-free survival.
- To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
研究の種類
介入
入学 (実際)
60
段階
- フェーズ2
- 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
-
-
Florida
-
Jacksonville、Florida、アメリカ、32207
- Baptist Cancer Institute - Jacksonville
-
Jacksonville、Florida、アメリカ、32207
- Integrated Community Oncology Network at Southside Cancer Center
-
Jacksonville、Florida、アメリカ、32258
- Baptist Medical Center South
-
Jacksonville Beach、Florida、アメリカ、32250
- Integrated Community Oncology Network
-
Orange Park、Florida、アメリカ、32073
- Integrated Community Oncology Network - Orange Park
-
Palatka、Florida、アメリカ、32177
- Florida Cancer Center - Palatka
-
Saint Augustine、Florida、アメリカ、32086
- Flagler Cancer Center
-
-
Michigan
-
Kalamazoo、Michigan、アメリカ、49007
- Bronson Methodist Hospital
-
Kalamazoo、Michigan、アメリカ、49001
- Borgess Medical Center
-
Kalamazoo、Michigan、アメリカ、49007-3731
- West Michigan Cancer Center
-
-
Missouri
-
Kansas City、Missouri、アメリカ、64131
- CCOP - Kansas City
-
Saint Louis、Missouri、アメリカ、63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
-
-
Nevada
-
Las Vegas、Nevada、アメリカ、89106
- CCOP - Nevada Cancer Research Foundation
-
-
New Jersey
-
Edison、New Jersey、アメリカ、08818
- John F. Kennedy Medical Center
-
-
Ohio
-
Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic Taussig Cancer Center
-
-
Oregon
-
Milwaukie、Oregon、アメリカ、97222
- Providence Milwaukie Hospital
-
Portland、Oregon、アメリカ、97213-2967
- Providence Cancer Center at Providence Portland Medical Center
-
Portland、Oregon、アメリカ、97225
- CCOP - Columbia River Oncology Program
-
Portland、Oregon、アメリカ、97225
- Providence St. Vincent Medical Center
-
-
Pennsylvania
-
Philadelphia、Pennsylvania、アメリカ、19107-5541
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
-
-
South Carolina
-
Charleston、South Carolina、アメリカ、29425
- Hollings Cancer Center at Medical University of South Carolina
-
-
Utah
-
Murray、Utah、アメリカ、84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
-
Provo、Utah、アメリカ、84604
- Utah Valley Regional Medical Center - Provo
-
-
Washington
-
Vancouver、Washington、アメリカ、98668
- Southwest Washington Medical Center Cancer Center
-
-
Wisconsin
-
Menomonee Falls、Wisconsin、アメリカ、53051
- Community Memorial Hospital Cancer Care Center
-
Milwaukee、Wisconsin、アメリカ、53226
- Medical College of Wisconsin Cancer 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:
- Primary central nervous system (CNS) lymphoma [B-cell, Cluster of Differentiation 20 (CD20) antigen positive] based on positive biopsy or cerebrospinal fluid (CSF) or vitreous cytology (in association with measurable intraparenchymal tumor). Cytology must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population.
- Life expectancy ≥ 8 weeks;
- Zubrod performance status of 0-2;
- Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age) x wt (kg)/(Cr[mg/dl]x 72); Bilirubin, serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal;
- Patients must sign a study-specific informed consent prior to study entry.
- Age ≥ 18
Exclusion criteria:
- Evidence of systemic lymphoma;
- Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years;
- Prior radiotherapy to the brain or head/neck;
- Prior chemotherapy;
- History of idiopathic sensitivity to any of the drugs to be used;
- Active infectious process;
- Seropositive for HIV, AIDS, or post-organ transplant;
- Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus.
- Active hepatitis B.
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：非ランダム化
- 介入モデル：順次割り当て
- 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：Phase I: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
他の名前：
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
|
|
実験的：Phase I: Temozolomide 150 mg
Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
他の名前：
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Temozolomide 150 mg/m^2 by mouth per day for five days on weeks 4 and 8.
|
|
実験的：Phase I: Temozolomide 200 mg
Rituximab, methotrexate, temozolomide 200 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
他の名前：
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Temozolomide 200 mg/m^2 per day by mouth for five days on weeks 4 and 8.
|
|
実験的：Phase II: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
|
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle.
Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion.
Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends).
A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
他の名前：
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
|
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 |
|---|---|---|
|
Number of Phase I Participants Experiencing Toxicity
時間枠：From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
|
A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide.
Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy.
If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15.
Any grade 5 toxicity would result in immediate suspension of accrual.
|
From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
|
|
Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
時間枠：Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
|
Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method.
Patients last known to be alive are censored at the date of last contact.
(Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
|
Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
時間枠：From start of treatment to 10 weeks if RT received, to 15 weeks if not.
|
Tumor response was centrally reviewed.
Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease.
(Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
|
From start of treatment to 10 weeks if RT received, to 15 weeks if not.
|
|
Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)
時間枠：Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
|
Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology.
The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid.
Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored).
Progression-free survival rates are estimated using the Kaplan-Meier method.
(Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions.
)
|
Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
|
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。
捜査官
- スタディチェア：Jon Glass, MD、Sidney Kimmel Cancer Center at Thomas Jefferson University
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
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
2003年7月1日
一次修了 (実際)
2016年12月1日
研究の完了 (実際)
2016年12月1日
試験登録日
最初に提出
2003年9月10日
QC基準を満たした最初の提出物
2003年9月10日
最初の投稿 (見積もり)
2003年9月11日
学習記録の更新
投稿された最後の更新 (実際)
2018年2月7日
QC基準を満たした最後の更新が送信されました
2018年2月1日
最終確認日
2018年2月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- RTOG-0227
- CDR0000301563
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。