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

German CLL Study Group

Status and phase: Completed; Phase 3

Conditions: Anemia; Chronic Lymphocytic Leukemia

Treatments: Drug: Fludarabine mono; Biological: Fludarabine plus Darbopoetin

Study type: Interventional

Funder types: Other

Identifiers

NCT00281892

CLL9

EU-20561

GCLLSG-CLL9

AMGEN-GCLLSG-CLL9

2005-003014-15 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 97 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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97 participants in 2 patient groups

Fludarabine plus Darbopoetin

Experimental group

Description:

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles and 500 mcg of darbepoetin alfa subcutaneously every 3 weeks

Treatment:

Biological: Fludarabine plus Darbopoetin

fludarabine mono

Active Comparator group

Description:

Group 1 - Patients with an initial Hb-value of less than 12 g/dl receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles with no additional growth factor support. Group 2 - Patients with an initial Hb-value more than 12 g/dl start to receive fludarabine (30 mg/m² intravenously on day 1, 3, 5; repeated every 28 days for 6 cycles . Patients of group 2 will be eventually randomized at later timepoints, if the Hb-value drops below 12 g/dl. Randomized patients will receive either 500 mcg darbepoetin alfa subcutaneously every 3 weeks or continue therapy with fludarabine without additional administration of darbepoetin alfa.

Treatment:

Drug: Fludarabine mono