Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

OBJECTIVES: * Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide. * Compare the response rate and duration of remission in patients treated with these regimens. * Compare the toxic effects of these regimens in these patients. * Compare the quality of life of patients treated with these regimens. * Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients. * Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens. OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization. Depending on response, some patients may also participate in a second randomization to one of two treatment arms. * First randomization: * Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year. * Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. * Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization. * Second randomization: * Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay. * Arm II: Treatment is physician's choice, which may include any of the options in arm I. Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter. Patients are followed annually for survival. PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study within 6-7 years.