Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop
 cancer cells from dividing so they stop growing or die. Biological therapies such as
 thalidomide use different ways to stimulate the immune system and stop cancer cells from
 growing. Combining fludarabine with thalidomide may kill more cancer cells.

 PURPOSE: This phase I/II trial is studying the side effects and best dose of thalidomide when
 given together with fludarabine and to see how well they work in treating patients with newly
 diagnosed B-cell chronic lymphocytic leukemia.
OBJECTIVES:

 -  Determine the safety and efficacy of fludarabine and thalidomide in patients with newly
 diagnosed B-cell chronic lymphocytic leukemia.

 -  Determine the overall response rate (complete and partial) in patients treated with this
 regimen.

 -  Determine the duration of response in patients treated with this regimen.

 OUTLINE: This is an open-label, phase I, dose-escalation study of thalidomide followed by a
 phase II study.

 -  Phase I: Beginning on day 1, patients receive oral thalidomide once daily for up to 6
 months. Beginning on day 7, patients also receive fludarabine IV over 30 minutes daily
 for 5 days. Treatment with fludarabine repeats every 28-35 days for up to 6 courses.
 Treatment continues in the absence of disease progression or unacceptable toxicity.

 Cohorts of 3-6 patients receive escalating doses of thalidomide until the maximum tolerated
 dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
 of 6 patients experience dose-limiting toxicity.

 -  Phase II: Patients receive fludarabine and thalidomide as in phase I at the MTD.

 Patients are followed at 4 weeks, every 3 months for 2 years, and then every 4 months for 2
 years.

 PROJECTED ACCRUAL: Up to 45 patients (≥ 9 for the phase I portion and ≤ 36 for the phase II
 portion) will be accrued for this study within 8 years.
DISEASE CHARACTERISTICS:

 -  Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) based on the
 following criteria:

 -  Peripheral blood lymphocytosis > 5,000/mm^3

 -  Co-expression of CD5, CD19 or CD20, and CD23 surface antigens

 -  Clonal kappa or lambda light chain expression

 -  No recurrent or refractory CLL

 -  No other lymphoproliferative diseases or diseases due to transformation of CLL, such
 as prolymphocytic leukemia or Richter's syndrome

 PATIENT CHARACTERISTICS:

 Age

 -  18 and over

 Performance status

 -  Karnofsky 60-100%

 Life expectancy

 -  At least 12 weeks

 Hematopoietic

 -  See Disease Characteristics

 Hepatic

 -  Bilirubin < 1.5 mg/dL

 -  AST < 2.5 times upper limit of normal

 Renal

 -  Creatinine ≤ 1.5 mg/dL

 Cardiovascular

 -  No cardiac arrhythmia within the past 6 months

 -  No myocardial infarction within the past 6 months

 Other

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use at least 1 highly active and 1 additional method of
 contraception for 4 weeks before, during, and for at least 4 weeks after study
 treatment

 -  Patients must have sufficient mental capacity to understand the study explanation and
 provide informed consent

 -  No other malignancy within the past 5 years except basal cell skin cancer or carcinoma
 in situ of the cervix

 -  No active serious infection uncontrolled by antibiotics

 -  No medical condition or reason that would preclude study participation

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  Not specified

 Chemotherapy

 -  Not specified

 Endocrine therapy

 -  Not specified

 Radiotherapy

 -  Not specified

 Surgery

 -  Not specified

 Other

 -  No prior therapy for CLL