Rituximab, Temozolomide, and Methylprednisolone in Treating Patients With Recurrent Primary CNS Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

- Determine the response rate in patients with recurrent primary CNS non-Hodgkin's
lymphoma treated with rituximab, temozolomide, and methylprednisolone.

Secondary

- Determine the overall and 6-month progression-free survival of patients treated with
this regimen.

OUTLINE: Induction therapy: Patients receive rituximab IV over 30-60 minutes on days 1, 8,
15, and 22 and oral temozolomide daily on days 1-7 and 15-21. After day 28, patients with
stable disease or better proceed to consolidation therapy.

Consolidation therapy: Patients receive oral temozolomide daily on days 1-5. Treatment
repeats every 28 days for up to 6 courses. Patients achieving a complete remission proceed to
maintenance therapy.

Maintenance therapy: Patients receive methylprednisolone IV over 2 hours on day 1. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately
13.3 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed primary CNS non-Hodgkin's lymphoma by brain biopsy, positive
cerebrospinal fluid cytology, or vitrectomy

- Recurrent disease

- Measurable disease, define as bi-dimensionally measurable lesions with clearly defined
margins by brain MRI or CT scan

- Radiographical evidence of tumor progression by MRI or CT scan

- Steroid therapy must be stable for 5 days prior to scan

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks

Hematopoietic

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

- SGOT < 2 times upper limit of normal (ULN)

- Bilirubin < 2 times ULN

- No active or latent hepatitis B infection

Renal

- Creatinine < 1.5 mg/dL OR

- Creatinine clearance ≥ 60 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other malignancy within the past 3 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix

- No uncontrolled significant medical illness that would preclude study treatment

- No active infection

- No active HIV infection

- No concurrent disease that would dangerously alter drug metabolism or obscure toxicity

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 7 days since prior interferon or thalidomide

- No concurrent prophylactic filgrastim (G-CSF)

- No concurrent immunotherapy

Chemotherapy

- No prior temozolomide

- At least 14 days since prior methotrexate

- At least 21 days since prior procarbazine

- At least 42 days since prior nitrosoureas

- No other concurrent chemotherapy

Endocrine therapy

- See Disease Characteristics

- At least 7 days since prior tamoxifen

- No concurrent hormonal therapy

Radiotherapy

- No concurrent radiotherapy

Surgery

- Not specified

Other

- Recovered from all prior therapy

- At least 28 days since prior investigational agents

- At least 28 days since other prior cytotoxic therapy

- At least 7 days since other prior non-cytotoxic agents (e.g., tretinoin)
(radiosenitizers allowed)

- No other concurrent investigational drugs