A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-dose Methotrexate (MTX)-Based Chemo-immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy
研究概览
简要总结
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. Radiation therapy uses high-energy x-rays to kill cancer cells. Motexafin gadolinium may make cancer cells more sensitive to radiation therapy and combination chemotherapy. Giving motexafin gadolinium together with chemotherapy, rituximab, and radiation therapy may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects of giving motexafin gadolinium together with combination chemotherapy, rituximab, and whole-brain radiation therapy and to see how well it works in treating patients with newly diagnosed primary central nervous system lymphoma.
详细描述
OBJECTIVES:
Primary
- Determine the safety and efficacy of motexafin gadolinium (MGd) combined with high-dose methotrexate-based chemotherapy and radiotherapy in patients with newly diagnosed primary CNS lymphoma.
- Determine the toxicity of MGd and rituximab combined with high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) in these patients.
- Determine the toxicity of MGd in combination with whole-brain radiotherapy (WBRT) in these patients.
- Determine the tumor-selective uptake of MGd.
Secondary
- Determine the overall response rate (complete remission [CR] and partial remission [PR]) in patients treated with pre-radiotherapy and chemo-immunotherapy (R-MPV with MGd).
- Determine the complete response rate in patients treated with this regimen.
- Determine the overall response rate (CR and PR) in patients who complete all MGd combined with high-dose methotrexate-based chemotherapy and WBRT.
- Determine the event-free and overall survival at 1 year of patients treated with this regimen.
- Determine the progression-free survival at 1 year of patients treated with this regimen.
- Evaluate the neurotoxicity of R-MVP with MGd based on pre- and post-treatment neuropsychologic testing.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed primary CNS lymphoma (PCNSL) diagnosed by brain biopsy, CSF cytology, or vitreal biopsy
- •Newly diagnosed disease
- •Patients who have an inconclusive biopsy or who are not candidates for biopsy may be eligible provided they have a typical cranial MRI or CT scan (defined as the presence of hypo-, iso- or hyperdense parenchymal contrast-enhancing, usually homogeneously) mass lesion(s) and meet at least one of the following criteria:
- •Positive cerebrospinal fluid cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
- •Biopsy of the vitreous or uvea demonstrating non-Hodgkin lymphoma
- •Measurable (defined as reproducibly measurable disease in two perpendicular dimensions on radiologic study) or evaluable disease
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-3
- •Life expectancy ≥ 8 weeks
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ 2.0 mg
- •SGOT ≤ 2 times upper limit of normal
- •Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 cc/min
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for 6 months after completion of study therapy
- •HIV negative
- •No other active primary malignancy with the exception of basal cell carcinoma of the skin or cervical carcinoma in situ
- •PRIOR CONCURRENT THERAPY:
- •No prior cranial irradiation
- •No prior chemotherapy for CNS lymphoma
排除标准
- 未提供
结局指标
主要结局
Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy
时间窗: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
To evaluate toxicity of motexafin gadolinium (MGd) and rituximab to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy at Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
Toxicity of MGd added to whole-brain radiotherapy (WBRT)
时间窗: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
To evaluate the toxicity of MGd added to whole-brain radiotherapy (WBRT).
Tumor-selective uptake of MGd
时间窗: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
To evaluate Tumor-selective uptake of MGd
次要结局
- Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd)(Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.)
- Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd)(Every 3 months after completion of treatment, exams every 3 months for the first year then every 4 - 6 months thereafter.)
- Overall survival at 1 year(Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.)
- Event-free survival at 1 year(Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.)
- Progression-free survival at 1 year(Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.)
- Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing(At baseline)