Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Non-Hodgkin's Lymphoma

• 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.