Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Gemcitabine in Treating Patients With Previously Untreated Aggressive Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

• Compare the complete response rate (confirmed or unconfirmed) in patients with previously untreated aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with vs without gemcitabine.

Secondary

• Compare the safety profile of these regimens in these patients.
• Compare the feasibility of these regimens, defined as the proportion of courses given as scheduled, in these patients.
• Compare freedom from treatment failure in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, International Prognostic Index score (0-2 vs 3-5), and histology (B cell vs T cell). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral or IV prednisone on days 1-5.
• Arm II: Patients receive CHOP chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity or progressive disease. Patients achieving partial response or complete or unconfirmed complete response receive an additional 5 courses of therapy (for a total of 8 courses).

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

PROJECTED ACCRUAL: A total of 76-82 patients (38-41 per treatment arm) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) of 1 of the following WHO subtypes:

• Diffuse large B large cell lymphoma (including all clinical and morphologic variants)
• Grade 3 follicular lymphoma
• Extranodal T/NK cell lymphoma, nasal type
• Enteropathy-type T cell lymphoma
• Hepato-splenic T cell lymphoma
• Peripheral T cell lymphoma, unspecified
• Angioimmunoblastic lymphoma
• Anaplastic large cell lymphoma, systemic type
• Stage II-IV disease
• At least 1 site of measurable disease (e.g., lymph node or lymph node mass)
• The following subtypes are not allowed:

• Mantle cell lymphoma
• Burkitt's lymphoma
• Precursor B or T cell lymphoma
• Primary cutaneous B or T cell lymphoma
• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,000/mm^3
• Neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 2.5 times normal (unless due to lymphoma)
• ALT and AST < 2.5 times normal (unless due to lymphoma)

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No severe cardiac disease that would preclude study participation or limit life expectancy

Pulmonary

• FEV_1 and DLCO ≥ 75% of predicted (unless due to lymphoma)
• No severe pulmonary disease that would preclude study participation or limit life expectancy

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No severe neurologic or metabolic disease that would preclude study participation or limit life expectancy
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent monoclonal antibodies

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior cytotoxic agents
• No prior treatment for NHL
• No other concurrent anticancer therapy
• No other concurrent investigational drugs