Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma
- Determine the maximum tolerated dose of temozolomide in combination with methotrexate
and rituximab before fractionated whole brain radiotherapy in patients with primary
central nervous system lymphoma.
- Compare the 2-year survival rate of patients receiving this chemotherapy regimen before
radiotherapy and temozolomide after radiotherapy to that of patients treated on
- Compare the tumor response rates of patients treated with this chemotherapy regimen
before radiotherapy to that of patients treated on Radiation Therapy Oncology Group
- Determine the progression-free survival of patients treated with this regimen.
- Determine the acute and long-term neurologic toxicity of this regimen in these
- Determine the quality of life of patients treated with this regimen.
OUTLINE: This is a phase I dose-escalation study of temozolomide in combination with
methotrexate and rituximab before radiotherapy, followed by a phase II study.
- Pre-radiotherapy chemotherapy: Patients receive rituximab IV 3 days prior to the first
course of methotrexate. Patients then receive methotrexate IV over 4 hours on weeks 1,
3, 5, 7, and 9 (for a total of 5 doses). Patients also receive oral temozolomide daily
for 5 days on weeks 4 and 8.
Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which no more than 0 of 3 or 1
of 6 patients experience dose-limiting toxicity.
- Radiotherapy: Patients undergo whole brain radiotherapy daily for 5 days on weeks 11,
12, and 13.
- Post-radiotherapy chemotherapy: Patients receive oral temozolomide once daily on days
1-5 beginning at week 14. Treatment repeats every 28 days for 10 courses in the absence
of unacceptable toxicity.
- Patients receive treatment as in phase I at the MTD of temozolomide. Treatment
continues in the absence of unacceptable toxicity.
Quality of life is assessed at baseline, at weeks 10 and 13, every 2 months during
post-radiotherapy temozolomide therapy, at the end of therapy, every 3 months for 2 years,
every 6 months for 3 years, and then annually thereafter.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
PROJECTED ACCRUAL: A total of 52-64 patients (up to 18 patients for phase I and 46 patients
for phase II) will be accrued for this study within 19 months.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity rate (Phase I)
From start of treatment to 10 weeks.
Jon Glass, MD
Kimmel Cancer Center (KCC)
United States: Federal Government
|CCOP - Kansas City||Kansas City, Missouri 64131|
|Bronson Methodist Hospital||Kalamazoo, Michigan 49007|
|West Michigan Cancer Center||Kalamazoo, Michigan 49007-3731|
|Borgess Medical Center||Kalamazooaa, Michigan 49001|
|Medical College of Wisconsin Cancer Center||Milwaukee, Wisconsin 53226|
|John F. Kennedy Medical Center||Edison, New Jersey 08818|
|CCOP - Columbia River Oncology Program||Portland, Oregon 97225|
|Kimmel Cancer Center at Thomas Jefferson University - Philadelphia||Philadelphia, Pennsylvania 19107|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|Utah Valley Regional Medical Center - Provo||Provo, Utah 84604|
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|
|Baptist Cancer Institute - Jacksonville||Jacksonville, Florida 32207|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|CCOP - Nevada Cancer Research Foundation||Las Vegas, Nevada 89109-2306|
|Providence Milwaukie Hospital||Milwaukie, Oregon 97222|
|Providence Cancer Center at Providence Portland Medical Center||Portland, Oregon 97213-2967|
|Providence St. Vincent Medical Center||Portland, Oregon 97225|
|Southwest Washington Medical Center Cancer Center||Vancouver, Washington 98668|
|Jon and Karen Huntsman Cancer Center at Intermountain Medical Center||Murray, Utah 84157|
|Community Memorial Hospital Cancer Care Center||Menomonee Falls, Wisconsin 53051|
|Integrated Community Oncology Network||Jacksonville Beach, Florida 32250|
|Baptist Medical Center South||Jascksonville, Florida 32258|
|Florida Cancer Center - Palatka||Palatka, Florida 32177|
|Flagler Cancer Center||Saint Augustine, Florida 32086|
|Integrated Community Oncology Network - Orange Park||Orange Park, Florida 32073|
|Integrated Community Oncology Network at Southside Cancer Center||Jacksonville, Florida 32207|