Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma - Article
Clinical Trial: Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
This study is currently recruiting patients.
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: Phase I/II trial to study the effectiveness of combining methotrexate, rituximab, and temozolomide with radiation therapy in treating patients who have primary central nervous system lymphoma.
|Condition||Treatment or Intervention||Phase|
|primary central nervous system lymphoma || Drug: methotrexate |
Procedure: antibody therapy
Procedure: biological response modifier therapy
Procedure: monoclonal antibody therapy
Procedure: radiation therapy
|Phase I |
MedlinePlus related topics: Cancer; Cancer Alternative Therapy; Lymphoma; Neurologic Diseases
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Study of Chemotherapy Comprising Methotrexate, Rituximab, and Temozolomide Before Radiotherapy and Temozolomide After Radiotherapy in Patients With 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 protocol RTOG-9310.
- Compare the tumor response rates of patients treated with this chemotherapy regimen before radiotherapy to that of patients treated on RTOG-9310.
- Determine the progression-free survival of patients treated with this regimen.
- Determine the acute and long-term neurologic toxicity of this regimen in these patients.
- Determine the quality of life of patients treated with this regimen.
- 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, and then every 3 months for 2 years, every 6 months for 3 years, and annually for 5 years.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
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.
Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both
- Cytologically confirmed primary CNS lymphoma
- Based on positive biopsy, cerebrospinal fluid, or vitreous cytology (in association with measurable intraparenchymal tumor)
- B-cell type
- CD20+ disease
- Cytology must demonstrate lymphoma OR an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population
- No evidence of systemic lymphoma
PATIENT CHARACTERISTICS: Age
- 18 and over
- Zubrod 0-2
- At least 8 weeks
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- AST no greater than 2 times ULN
- Alkaline phosphatase no greater than 2 times ULN
- Creatinine clearance at least 50 mL/min
- No renal insufficiency
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No history of idiopathic sensitivity to any of the drugs in this study
- No active infection
- No known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab
PRIOR CONCURRENT THERAPY: Biologic therapy
- Not specified
- No prior chemotherapy
- Not specified
- No prior radiotherapy to the brain, head, or neck
- No prior organ transplantation
Location and Contact Information
Foundation for Cancer Research and Education, Phoenix, Arizona, 85013, United States; Recruiting
USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California, 90033-0804, United States; Recruiting
Baptist-South Miami Regional Cancer Program, Miami, Florida, 33176-2197, United States; Recruiting
Wendt Regional Cancer Center at Finley Hospital, Dubuque, Iowa, 52001, United States; Recruiting
West Michigan Cancer Center, Kalamazoo, Michigan, 49007, United States; Recruiting
CCOP - Kansas City, Kansas City, Missouri, 64131, United States; Recruiting
CCOP - Marshfield Clinic Research Foundation, Marshfield, Wisconsin, 54449, United States; Recruiting
Jon Glass, MD, Study Chair, Fox Chase Cancer Center
Record last reviewed: August 2003
Last Updated: March 10, 2005
Record first received: September 10, 2003
ClinicalTrials.gov Identifier: NCT00068250
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08
Cache Date: April 9, 2005