High-Dose Methotrexate Plus Steroid Followed by Concurrent Whole Brain Chemoradiation With Temozolomide for Immunocompetent Patients With Primary Central Nervous System Lymphoma - a Phase II Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- Primary : To evaluate objective tumor response rate
研究概览
简要总结
In this study we will test the hypothesis that concurrent chemoradiation (CCRT) with temozolomide after induction chemotherapy by conventional high-dose methotrexate (HD-MTX) plus dexamethasone may be an effective and well tolerated treatment for immunocompetent patients with PCSNL. Corticosteroid can effectively reduce brain edema and corticosteroid alone has resulted in complete or partial remission in about 40% patients with PCNSL. To enhance local disease control, CCRT with temozolomide will be used in the study. Temozolomide is a well-tolerated oral alkylating agent that is able to permeate the BBB. Concurrent temozolomide with WBRT has shown superior effect to WBRT alone for the treatment of metastatic brain tumors and glioblastoma multiforme. In addition, temozolomide has single-agent activity for PCNSL (21% CR in relapsed or refractory PCNSL in a phase II trial).
This is an open-label, non-randomized, multi-center phase II study. The primary end point of is the complete response rate. This study is a two-stage design for testing non-inferiority of the proposed treatment as compared to the approximately 80% response rate reported for conventional treatment. Assuming a non-inferiority margin of 20%, a sample size of 25 subjects, which provides an 80% power for establishment of non-inferiority. At the first stage, 15 subjects are to be enrolled. If equal to or more than 6 patients achieve complete response, the study would accrue additional 10 subjects. The treatment regimen is as follows.
Induction chemotherapy: MS regimen (repeated every 14 days, total 4 cycles)
- Methotrexate 3.5 g/m2 i.v. infusion 4 hours on day1
- Methylprednisolone 200 mg/m2/day i.v. infusion 30 minutes, on day1-4 Concurrent chemoradiotherapy (CCRT)
- Whole brain radiation therapy (WBRT) 2 Gy per fraction daily, 5 days per week Temozolomide 75 mg/m2/day orally daily, only on the days of WBRT
详细描述
5 PATIENT SELECTION 5.1 Eligibility Criteria
Patients must fulfill all the following criteria to be eligible for admission for the study:
- Histologically proven central nervous system lymphoma of brain parenchyma with or without leptomeningeal involvement.
- No evidence of systemic lymphoma.
- Age between 18 years and 75 years.
- With at least one measurable lesion, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm. See Section 10.2.1 for the evaluation of measurable disease.
- Laboratory requirements :
- Hematology: Neutrophils≧ 1500/mm3, Hemoglobin≧ 10 g/dL, and Platelet count≧ 100000/mm3.
- Hepatic function: Total bilirubin level≦ 1.5x upper normal limit (UNL), ALT (SGPT) and AST (SGOT)≦ 2.5 x UNL.
- Renal function: Creatinine≦ 1.5 mg/dL.
- No prior malignancy (excluding in situ carcinoma of the cervix or non- melanomatous skin cancer) unless disease free for at least 5 years.
- Signed informed consent.
- Patients must be accessible for treatment and follow-up. 5.2 Ineligibility Criteria Patient meets any of the following will be excluded form the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must fulfill all the following criteria to be eligible for admission for the study:
- •Histologically proven central nervous system lymphoma of brain parenchyma with or without leptomeningeal involvement.
- •No evidence of systemic lymphoma.
- •Age between 18 years and 75 years.
- •With at least one measurable lesion, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm. See Section 10.2.1 for the evaluation of measurable disease.
- •Laboratory requirements :
- •Hematology: Neutrophils≧ 1500/mm3, Hemoglobin≧ 10 g/dL, and Platelet count≧ 100000/mm
- •Hepatic function: Total bilirubin level≦ 1.5x upper normal limit (UNL), ALT (SGPT) and AST (SGOT)≦ 2.5 x UNL.
- •Renal function: Creatinine≦ 1.5 mg/dL.
- •No prior malignancy (excluding in situ carcinoma of the cervix or non- melanomatous skin cancer) unless disease free for at least 5 years.
- •Signed informed consent.
- •Patients must be accessible for treatment and follow-up.
排除标准
- •Patient meets any of the following will be excluded form the study.
- •Patients who are seropositive for HIV, AIDS, use of immunosuppressant or who are post organ transplant are not eligible.
- •Previously treated with chemotherapy, radiotherapy or other investigational agents. Patients with corticosteroid use are considered eligible.
- •With ocular involvement or with any lesion beyond brain parenchyma except leptomeningeal.
- •Pregnant, or lactating patients; patients of childbearing potential must implement adequate contractive measures during study participation.
- •Other serious illness or medical conditions:
- •Congestive heart failure or unstable angina pectoris. High risk uncontrolled arrhythmias.
- •Uncontrolled infection (active serous infections that are not controlled by antibiotics.
- •Concurrent treatment with any other experimental drugs.
结局指标
主要结局
Primary : To evaluate objective tumor response rate
次要结局
- Secondary : To assess toxicity profile
- To assess time to disease progression