Trial Information

Chronic Lymphocytic Leukemia Trial 4: A Randomized Comparison of Chlorambucil, Fludarabine and Fludarabine Plus Cyclophosphamide

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.