OBJECTIVES:

• Determine the response rate, progression-free survival, and overall survival of patients with previously untreated aggressive CD20+ B-cell diffuse large cell or immunoblastic large cell lymphoma treated with rituximab, doxorubicin, etoposide, vincristine, prednisone, and cyclophosphamide.
• Determine the toxic effects of this regimen in these patients.
• Correlate tumor proliferation rate (MIB-1), bcl-2 expression, and p53 overexpression with complete response rate, progression-free survival, and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1; doxorubicin IV continuously, etoposide IV continuously, and vincristine IV continuously on days 1-4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV on day 5. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients with complete or partial response receive 2 additional courses.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage II, III, or IV diffuse large cell lymphoma and WHO variants

  • CD20+ large B-cell lymphoma, including those with immunoblastic features
  • CD20+ thymic B-cell lymphoma
  • No evidence of indolent lymphoma
  • No mantle cell lymphomas or equivocal B-cell lymphomas that express markers of mantle cell lymphoma (e.g., cyclin D) or other subtypes
• No known lymphomatous involvement of the CNS, including the parenchyma or leptomeninges

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• CALGB 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3*
• Platelet count at least 100,000/mm3* NOTE: * Unless due to lymphoma

Hepatic:

• Bilirubin no greater than 2.0 mg/dL* NOTE: * Unless due to lymphoma or Gilbert's disease

Renal:

• Creatinine no greater than 1.5 mg/dL* NOTE: * Unless due to lymphoma

Cardiovascular:

• LVEF greater than 45%
• No ischemic heart disease
• No myocardial infarction or congestive heart failure within the past year

Other:

• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Prior short-course of glucocorticoids allowed
• No concurrent hormones except for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent steroids except for adrenal failure
• No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy:

• Prior limited-field radiotherapy allowed

Surgery:

• Not specified