• Overall survival [ Designated as safety issue: No ]
• Response [ Designated as safety issue: No ]

• Overall survival
• Response

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 cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of anticancer drugs by making cancer cells more sensitive to the drugs. Combining rituximab and combination chemotherapy with oblimersen may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying rituximab and combination chemotherapy to see how well they work compared to oblimersen, rituximab, and combination chemotherapy in treating patients with advanced diffuse large B-cell non-Hodgkin's lymphoma.

OBJECTIVES:

• Compare the 1-year progression-free survival probability rate in patients with low- or low-intermediate-risk advanced diffuse large B-cell non-Hodgkin's lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without oblimersen.
• Compare the response (complete, unconfirmed complete, and partial) in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the 1-year progression-free survival and response rate in a subset of patients overexpressing bcl-2 protein treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age-adjusted International Prognostic Index (0 vs 1). Patients are randomized to 1 of 2 treatment arms. (Arm I closed to accrual as of 9/21/04.)

• Arm I (closed to accrual as of 9/21/04): Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
• Arm II: Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.

In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for up to 5 years.

PROJECTED ACCRUAL: A total of 160 patients (80 per treatment arm) (arm I closed to accrual as of 9/21/04) will be accrued for this study within 2 years.

• Biological: oblimersen sodium
• Biological: rituximab
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: prednisone
• Drug: vincristine sulfate

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma

  • Stage III, IV, or bulky stage II disease
  • Needle aspiration or cytology not considered adequate for biopsy
• CD20-positive disease
• Previously untreated disease
• Bidimensionally measurable disease

• No prior diagnosis of indolent lymphoma, including histologic transformation

  • Nodal diffuse large cell lymphoma with bone marrow involvement and small lymphocytes allowed
• International Prognostic Index 0-1
• No clinical evidence of CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 to 59

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• Cardiac ejection fraction ≥ 45% by MUGA or ECHO
• No significant cardiac abnormalities

Other

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

• No other malignancy within the past 5 years except any of the following:

  • Adequately treated basal cell or squamous cell skin cancer
  • Carcinoma in situ of the cervix
  • Adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior antibody therapy for lymphoma

Chemotherapy

• No prior chemotherapy for lymphoma

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for lymphoma

Surgery

• No prior solid organ transplantation

Other

• No concurrent supplemental oxygen therapy
• Concurrent enrollment on SWOG-8947 and/or SWOG-8819 allowed