Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 26
- 主要终点
- Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: rituximab (Drug)
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.
干预措施: methotrexate (Drug)
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.
干预措施: temozolomide 100 mg/m^2 (Drug)
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.
干预措施: radiation therapy (Radiation)
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.
干预措施: post-radiation therapy temozolomide (Drug)
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.
干预措施: rituximab (Drug)
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.
干预措施: methotrexate (Drug)
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.
干预措施: temozolomide 150 mg/m^2 (Drug)
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.
干预措施: radiation therapy (Radiation)
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.
干预措施: post-radiation therapy temozolomide (Drug)
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.
干预措施: rituximab (Drug)
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.
干预措施: methotrexate (Drug)
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.
干预措施: temozolomide 200 mg/m^2 (Drug)
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.
干预措施: radiation therapy (Radiation)
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.
干预措施: post-radiation therapy temozolomide (Drug)
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.
干预措施: rituximab (Drug)
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.
干预措施: methotrexate (Drug)
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.
干预措施: temozolomide 100 mg/m^2 (Drug)
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.
干预措施: radiation therapy (Radiation)
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.
干预措施: post-radiation therapy temozolomide (Drug)
结局指标
主要结局
Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
时间窗: 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. )
Number of Phase I Participants Experiencing Toxicity
时间窗: 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.
次要结局
- Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)(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)(Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.)