Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia

A Phase II Study of Oral Fludarabine Phosphate in Patients With Previously Untreated B-Cell 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.

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