• Overall survival assessed by clinical and radiographic response [ Designated as safety issue: No ]
• Progression-free survival assessed by clinical and radiographic response from first day of treatment until tumor progression [ Designated as safety issue: No ]
• Quality of life assessed by EORTC QOL before treatment and then every 3 months [ Designated as safety issue: No ]
• Ototoxicity assessed by audiology hearing test done monthly during treatment [ Designated as safety issue: Yes ]
• Effect of sodium thiosulfate (STS) on granulocytes and erythrocytes assessed by complete blood count lab values done weekly during treatment [ Designated as safety issue: No ]
• Measure concentration of rituximab in serum and cerebrospinal fluid by rituximab test assay once at the start of treatment [ Designated as safety issue: No ]

• Overall survival assessed by clinical and radiographic response
• Progression-free survival assessed by clinical and radiographic response from first day of treatment until tumor progression
• Quality of life assessed by EORTC QOL before treatment and then every 3 months
• Ototoxicity assessed by audiology hearing test done monthly during treatment
• Effect of sodium thiosulfate (STS) on granulocytes and erythrocytes assessed by complete blood count lab values done weekly during treatment
• Measure concentration of rituximab in serum and cerebrospinal fluid by rituximab test assay once at the start of treatment

RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.

OBJECTIVES:

Primary

• Determine the efficacy of rituximab, carboplatin, cyclophosphamide, and etoposide or etoposide phosphate administered in conjunction with osmotic blood-brain barrier disruption and high-dose sodium thiosulfate and cytarabine, in terms of complete response rate, in patients with refractory or recurrent primary CNS lymphoma.

Secondary

• Determine the overall survival and 2-year progression-free survival of patients treated with this regimen.
• Determine the quality of life and cognitive function of patients treated with this regimen.
• Determine the neurotoxicity of this regimen in these patients.
• Determine the percentage of patients with ototoxicity over time after treatment with this regimen.
• Determine the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1. On days 2 and 3, patients receive carboplatin intra-arterially over 10 minutes, cyclophosphamide IV over 10 minutes, and etoposide or etoposide phosphate IV over 10 minutes in conjunction with blood-brain barrier disruption. Patients also receive high-dose sodium thiosulfate IV over 15 minutes administered 4 and 8 hours after carboplatin on days 2 and 3 and intraventricular or intrathecal cytarabine on day 14. Beginning 48 hours after the last dose of chemotherapy, patients receive filgrastim (G-CSF)* subcutaneously (SC) daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses.

NOTE: * Alternatively, patients may receive a single dose of pegfilgrastim SC, administered 48 hours after the completion of chemotherapy

Patients with intraocular lymphoma also receive methotrexate intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam; once weekly for 1 month; and then monthly for 1 year.

Quality of life is assessed at baseline, every 3 months during treatment, at 30 days, every 6 months for 1 year, and then annually thereafter.

Patients are followed monthly for 3 months, every 2 months for 8 months, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 11-25 patients will be accrued for this study within 2-3 years.

• Drug/Agent Toxicity by Tissue/Organ
• Lymphoma
• Thrombocytopenia

• Biological: filgrastim
• Biological: pegfilgrastim
• Biological: rituximab
• Drug: blood-brain barrier disruption chemotherapy
• Drug: carboplatin
• Drug: cyclophosphamide
• Drug: cytarabine
• Drug: etoposide
• Drug: etoposide phosphate
• Drug: sodium thiosulfate

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary CNS lymphoma documented by brain biopsy or cerebrospinal fluid or vitrectomy analysis
• CD20 positive disease
• Progressive or relapsed disease during or after completion of prior methotrexate-based chemotherapy
• No systemic lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 months to 75 years

Performance status

• ECOG 0-3 OR
• Karnofsky 30-100%

Life expectancy

• Not specified

Hematopoietic

• Hematocrit at least 25% (transfusion or epoetin alfa allowed)
• Absolute granulocyte count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3 OR at least lower limit of normal

Hepatic

• Bilirubin no greater than 2.0 times upper limit of normal

Renal

• Creatinine less than 1.8 mg/dL
• Creatinine clearance at least 30 mL/min

Cardiovascular

• Adequate cardiac function to tolerate general anesthesia

Pulmonary

• Adequate pulmonary function to tolerate general anesthesia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 2 months before and during study participation
• No known allergy to study agents
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy allowed

Surgery

• Prior surgery or biopsy allowed