Fludarabine and Darbepoetin Alfa in Treating Older Patients With Chronic Lymphocytic Leukemia

• Efficacy [ Designated as safety issue: No ]
• Anemia [ Designated as safety issue: No ]
• Transfusion requirements [ Designated as safety issue: No ]
• Quality of life [ Designated as safety issue: No ]
• Duration and frequency of hospitalization [ Designated as safety issue: No ]
• Event-free survival [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Medical-economical impact [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Darbepoetin alfa may cause the body to make more red blood cells. It is not yet known whether fludarabine is more effective with or without darbepoetin alfa in treating chronic lymphocytic leukemia.

PURPOSE: This phase III trial is studying fludarabine to see how well it works when given together with or without darbepoetin alfa in treating older patients with chronic lymphocytic leukemia.

OBJECTIVES:

• Compare the efficacy of fludarabine with or without darbepoetin alfa in geriatric patients with chronic lymphocytic leukemia and relevant comorbidities.
• Determine the effect of these regimens in reducing anemia, lowering the requirements of transfusion, and reducing the duration and frequency of hospitalization in these patients.
• Determine the quality of life of patients treated with these regimens.
• Determine event-free, progression-free, and overall survival of patients treated with these regimens.
• Evaluate the medical-economical aspects of these regimens in these patients

OUTLINE: This is a multicenter study. Patients are stratified according to hemoglobin value (< 12 g/dL [stratum 1] vs > 12 g/dL [stratum 2]). Patients are assigned to 1 of 2 treatment strata.

• Stratum 1: Patients receive fludarabine IV on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses. Patients also receive darbepoetin alfa subcutaneously once weekly for up to 6 weeks.
• Stratum 2: Patients receive fludarabine as in stratum 1. Quality of life is evaluated periodically.

PROJECTED ACCRUAL: A total of 348 patients will be accrued for this study.

• Anemia
• Leukemia

• Biological: darbepoetin alfa
• Drug: fludarabine phosphate

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:

  • Previously untreated disease
  • Progressive or relapsed CLL after treatment with nonpurine analog-containing regimens as chlorambucil or bendamustine hydrochloride

• Meets 1 of the following staging criteria:

  • Binet stage A disease with B symptoms requiring treatment

  • Binet stage B disease requiring treatment, meeting ≥ 1 of the following criteria:

    • Rapid disease progression
    • Enlarged lymph nodes and organs
    • Severe B symptoms
  • Binet stage C disease
• Must have comorbidities (i.e., CIRS score > 6)
• Must have restricted kidney function (i.e., creatinine clearance < 70mL/min)
• No transformation to aggressive non-Hodgkin's lymphoma (Richter's syndrome)

PATIENT CHARACTERISTICS:

• Life expectancy > 6 months
• Creatinine clearance > 30 mL/min
• No active second malignancy
• No active bacterial, viral, or fungal infection
• No conditions that would preclude substitution of iron
• No severe myocardial, coronary, or respiratory insufficiency
• No severe liver insufficiency
• No known hypersensitivity to darbepoetin alfa
• No cerebral dysfunction that would preclude participation in the required study procedures

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent participation in another clinical trial