Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
 so they stop growing or die. It is not yet known which regimen of chemotherapy is more
 effective for chronic lymphocytic leukemia.

 PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works
 compared to fludarabine and cyclophosphamide or fludarabine alone 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.
DISEASE CHARACTERISTICS:

 -  Diagnosis of B-cell chronic lymphocytic leukemia (CLL) requiring therapy and meeting
 the following criteria:

 -  Previously untreated disease

 -  Peripheral blood morphology, excluding other leukemia and low-grade lymphoma in
 leukemic phase

 -  Cell markers: CD5+, CD23+, SmIg (weak), CD79b-, FMC7-

 -  Persistent lymphocytosis (greater than 10,000/mm^3)

 -  At least 40% bone marrow infiltration

 -  Stage 0 or I progressive disease indicated by at least one of the following:

 -  Persistent rise in lymphocyte count with doubling time less than 12 months

 -  Downward trend in hemoglobin and/or platelet count

 -  At least 50% increase in size of liver and/or spleen and/or lymph nodes

 -  Appearance of lymphadenopathy, hepatomegaly, or splenomegaly

 -  Constitutional symptoms caused by disease

 -  Pyrexia

 -  Night sweats

 -  Weight loss OR

 -  Stage II or III

 PATIENT CHARACTERISTICS:

 Age:

 -  Not specified

 Performance status:

 -  Not specified

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  See Disease Characteristics

 Hepatic:

 -  Bilirubin no greater than 2 times upper limit of normal (ULN)*

 -  SGOT/SGPT no greater than 2 times ULN* NOTE: * Unless due to CLL

 Renal:

 -  Creatinine clearance at least 30 mL/min

 Other:

 -  No other cancer or life-threatening disease

 -  Not pregnant

 -  Fertile patients must use effective contraception during and for 6 months after study
 therapy

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  Not specified

 Chemotherapy

 -  Not specified

 Endocrine therapy

 -  No concurrent corticosteroids (e.g., dexamethasone) as antiemetics

 Radiotherapy

 -  Not specified

 Surgery

 -  Not specified