Pilot Study of MGd + High-dose MTX-Based Chemoimmunotherapy + RT for Newly Dx PCNSL
- Conditions
- LymphomaNeurotoxicityBrain and Central Nervous System Tumors
- Registration Number
- NCT00734773
- Lead Sponsor
- Northwestern University
- Brief Summary
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.
- Detailed Description
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.
OUTLINE:
* Tumor-selective imaging: Patients receive motexafin gadolinium (MGd) IV on days 1-2 beginning 1-2 weeks prior to induction therapy. They then undergo an MRI of the brain.
* Induction therapy: Patients receive methotrexate IV over 2-3 hours and vincristine IV on day 1 and rituximab IV over 5 hours and MGd IV over 30-60 minutes on day 8. Patients also receive oral procarbazine hydrochloride on days 1-7 of courses 1, 3, and 5. Treatment repeats every 14 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response receive an additional 2 courses of induction therapy.
* Chemoradiotherapy: Beginning 4 weeks after completion of induction therapy, patients undergo reduced-dose whole-brain radiotherapy for 6 weeks. Patients also receive MGd IV over 30-60 minutes, beginning 2-5 hours prior to radiotherapy, for 10 days and then every other day during radiotherapy.
* Consolidation therapy: After completion of chemoradiotherapy, patients receive cytarabine IV over 3 hours on days 1-2. Treatment repeats every 30 days for 2 courses.
After completion of study therapy, patients are followed every 3 months for the first year, every 3-4 months for the second year, every 4-6 months until the fifth year, and then annually thereafter.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy 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) 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 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
- Secondary Outcome Measures
Name Time Method 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. MRI scan will be done with each neurologic evaluation. Neuropsychologic evaluation will be repeated approximately 6 months after the completion of therapy and at 6 months intervals thereafter for total of 2 years.
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. Repeat CSF or ocular exam will be done 3 months after completion of treatment in those patients who had evidence of CSF or ocular involvement at diagnosis. CSF will be sampled at each visit. Ocular exams will occur every 3 months for the 1st year then every 4-6 months. Further exams will only be done as needed to rule out recurrent lymphoma.
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. To assess overall survival rate.
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. To assess event-free survival rate.
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. To assess progression-free survival rate.
Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing At baseline MR perfusion and MR spectroscopy at baseline and serially when MRI imaging is done to assess response rates using these alternate forms of imaging.