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.