• Time to treatment failure [ Designated as safety issue: No ]
  
• Progression-free survival rate [ Designated as safety issue: No ]
  
• Overall survival rate [ Designated as safety issue: No ]
  

• Clinical remission rate [ Designated as safety issue: No ]
  
• Molecular remission rate [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the overall survival rate, progression free survival rate, clinical and molecular remission rates, and time to treatment failure in patients with newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma treated with chlorambucil, mitoxantrone, and dexamethasone versus fludarabine, mitoxantrone, and dexamethasone.
• Compare the efficacy and tolerability of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Index score [low risk (score 1) vs intermediate low risk (score 2) vs intermediate high risk (score 3) vs high risk (score 4 or 5)]. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive mitoxantrone IV on day 1, oral chlorambucil on days 1-10, and oral dexamethasone on days 1-5.
• Arm II: Patients receive mitoxantrone and dexamethasone as in arm I and fludarabine IV on days 1-3.

Treatment continues every 4 weeks for 4-8 courses.

Patients are followed at 3, 6, and 12 months, every 6 months for 1 year, and then annually thereafter until clinical relapse.

PROJECTED ACCRUAL: A total of 500 patients (250 per arm) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically proven newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma

  • REAL classification grade I, II, or III

• Treatment necessity indicated by presence of the following:

  • B symptoms
  • Bone marrow failure
  • Bulky or progressive disease
  • Compression syndromes
• No CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• No autoimmune hemolytic anemia or active hemolysis
• Direct Coombs' negative

Hepatic:

• Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN)*
• Bilirubin no greater than 2.5 times ULN* NOTE: *Unless attributable to lymphoma

Renal:

• Creatinine no greater than 2.5 times ULN (unless attributable to lymphoma)

Cardiovascular:

• No severe cardiac failure
• Ejection fraction at least 45%

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for at least 6 months after study
• HIV negative
• No prior malignancy except carcinoma in situ of the cervix or squamous cell skin cancer
• No other serious medical disease that would limit lifespan or ability to tolerate chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent systemic corticosteroids

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No prior therapy