Combination Chemotherapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

OBJECTIVES:

• Compare the overall survival, failure free survival, disease specific survival, relapse free survival, and response rate in patients with aggressive non-Hodgkin's lymphoma treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).
• Compare the early and late toxicities of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1 and vincristine and bleomycin IV on day 8. Treatment continues every 14 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral prednisolone daily on courses 1 and 2 and every other day beginning on course 3 and continuing until the end of treatment.
• Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Treatment continues every 21 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, then every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 310 patients (155 per arm) will be accrued for this study over 5 years.

DISEASE CHARACTERISTICS:

• Histologically proven previously untreated bulky stage IA or stage IB-IV aggressive non-Hodgkin's lymphoma of 1 of the following types:

• Working formulation:

• Follicular large cell
• Diffuse mixed cell
• Diffuse large cell
• Diffuse immunoblastic OR
• REAL classification:

• Diffuse large B-cell
• Peripheral T-cell
• Measurable or evaluable disease
• Good prognosis defined as no more than one of the following:

• Stage III/IV disease
• LDH greater than upper limit of normal
• ECOG/WHO 2-4
• No lymphoblastic or Burkitt's lymphoma
• No CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 18 to 59

Performance status:

• See Disease Characteristics

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin, AST, and ALT no greater than 1.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.7 mg/dL

Cardiovascular:

• Ejection fraction at least 50% unless dysfunction attributable to lymphoma

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other concurrent serious uncontrolled medical conditions
• No other prior malignancy except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to more than 35% of hematopoietic sites
• Concurrent consolidation radiotherapy allowed

Surgery:

• Not specified