Lymphoma
Conditions
Keywords
primary central nervous system non-Hodgkin lymphoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as methotrexate and thiotepa, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining methotrexate with thiotepa in treating patients who have newly-diagnosed primary CNS lymphoma.
Detailed description
OBJECTIVES: * Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa. * Determine the duration of progression-free survival and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients. * Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients. OUTLINE: This is a multicenter study. Patients receive thiotepa IV over 15 minutes on day 1. Patients also receive methotrexate IV over 4 hours on days 1 (8 hours after thiotepa) and 14. Beginning 24 hours after the start of methotrexate infusion, patients receive leucovorin calcium IV or orally every 6 hours until rescue is achieved. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving disappearance of enhancement of disease on MRI receive an additional 28-day course followed by maintenance therapy comprising thiotepa and methotrexate once a month for 11 courses. Patients undergo neuro-ophthalmologic exams annually for 2 years. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study within 8-20 months.
Interventions
DRUGleucovorin calcium
DRUGmethotrexate
DRUGthiotepa
Sponsors
National Cancer Institute (NCI)
New Approaches to Brain Tumor Therapy Consortium
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary CNS lymphoma * Confirmed by 1 of the following: * Brain biopsy or resection * CSF cytology * Positive cytology or immunohistochemical diagnosis of monoclonality and measurable intracranial tumor * Vitreal biopsy * Measurable and contrast-enhancing disease on the postoperative, pretreatment MRI or CT scan * No radiographic evidence of ascites or pleural effusions PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic * Bilirubin no greater than 2.0 mg/dL * SGOT no greater than 4 times upper limit of normal Renal * Creatinine no greater than 2 mg/dL * Creatinine clearance at least 50 mL/min Other * Mini mental score of at least 15 * HIV negative * Able to achieve hydration * No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ * No allergy to methotrexate * No serious infection * No medical illness that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * No prior immunotherapy or biologic therapy for this disease Chemotherapy * No prior chemotherapy for this disease * No other concurrent chemotherapeutic agents Endocrine therapy * No prior hormonal therapy for this disease * Prior glucocorticoid therapy allowed Radiotherapy * No prior radiotherapy for this disease * No prior cranial irradiation Surgery * See Disease Characteristics Other * At least 1 week since prior salicylates, non-steroidal anti-inflammatory drugs, probenecid, folic acid, or sulfonamide medications * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete radiographic response | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of progression-free survival and overall survival | — |
| Toxicity | — |
| Association of tumor BCL-6 expression with response | — |
| Relationship among initial response to steroids, response to chemotherapy, and survival | — |
Countries
United States
Outcome results
None listed