Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of fludarabine in treating patients who have chronic lymphocytic leukemia that has not been previously treated.

OBJECTIVES:

* Determine the overall response rate (complete and partial) in patients with previously untreated B-cell chronic lymphocytic leukemia treated with oral fludarabine.
* Determine the molecular complete response rate in patients who achieve a clinical or immunophenotypic complete response when treated with this drug.
* Determine the progression-free and treatment-free survival of patients treated with this drug.
* Determine the toxicity of this drug in these patients.
* Determine the baseline incidence of defined genetic abnormalities in patients treated with this drug.
* Determine the prognostic and predictive significance of defined genetic abnormalities in patients with respect to response to treatment with this drug.
* Determine the prognostic and predictive significance of immunophenotypic profile of patients with respect to response to treatment with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral fludarabine on days 1-5. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission after 6 courses do not receive further study therapy.

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

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study within 2 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL)

  * Previously untreated
  * Rai stage I, II, III, or IV
  * Requiring systemic therapy
* Persistent lymphocytosis of greater than 5,000/mm\^3

  * Morphologically mature lymphocytes
* Monoclonal B-cell population

  * CD19/CD5/CD23 positive with kappa or lambda light chain restriction by immunophenotyping
* No other lymphoproliferative disorders including prolymphocytic leukemia, mantle cell lymphoma, progression to aggressive B-cell lymphoma, or Richter's syndrome
* No clinical autoimmune hematologic complication of CLL including Coomb's-positive hemolytic anemia or immune thrombocytopenia

  * Positive Coomb's test allowed if no clinical hemolysis

PATIENT CHARACTERISTICS:

Age

* 16 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 6 months

Hematopoietic

* See Disease Characteristics

Hepatic

* Bilirubin no greater than 2 times upper limit of normal (ULN)
* AST and/or ALT no greater than 2 times ULN

Renal

* Creatinine no greater than 2 times ULN

Other

* Accessible for treatment and follow-up
* No known HIV infection
* No active bacterial, viral, or fungal infection requiring systemic antibiotics
* No conditions requiring corticosteroid therapy
* No history of other malignancies except for the following:

  * Adequately treated nonmelanoma skin cancer
  * Curatively treated carcinoma in situ of the cervix
  * Other solid tumors curatively treated with no evidence of disease within the past 5 years
* No other major medical illness that would preclude study
* No known hypersensitivity to fludarabine or its components
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy including monoclonal antibody therapy
* No concurrent autologous or allogeneic stem cell or bone marrow transplantation

Chemotherapy

* No other concurrent cytotoxic drugs

Endocrine therapy

* No concurrent corticosteroids except inhaled or topical corticosteroids

  * No concurrent corticosteroids for nausea prophylaxis

Radiotherapy

* No prior radiotherapy affecting more than 25% of bone marrow and/or involving the pelvic area
* No concurrent radiotherapy

Surgery

* Not specified

Other

* At least 4 weeks since prior investigational agents
* No other concurrent investigational agents