Bendamustine demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. This study assesses its efficacy in patients with chronic lymphocytic leukemia pre-treated with an alkylator, in comparison to fludarabine.

Patients with relapsed chronic lymphocytic leukemia requiring treatment after one previous systemic regimen (usually chlorambucil-based) are randomized to either receive bendamustine 100 mg/m² on days 1 and 2 of a 4-week cycle, or standard fludarabine treatment consisting of 25 mg/m² on days 1 to 5 every four weeks. The primary objective was to achieve non-inferior progression-free survival with bendamustine.

Inclusion Criteria:

• histologically or immunologically confirmed chronic B-cell leukemia
• refractory (i.e. no response or progression during initial chemotherapy) or relapsed situation after first-line treatment regimen
• disease stage II-IV according to Rai or B/C according to Binet staging system, respectively
• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or better
• negative pregnancy test/ adequate method of contraception

Exclusion Criteria:

• T-CLL, PLL (prolymphocytic leukemia)
• presence of Richter's transformation
• first-line treatment containing either fludarabine or bendamustine
• acute infections or distinctly reduced organ function precluding the application of chemotherapy, as for pulmonary, heart, liver (total bilirubin > 5mg/dl), renal system (creatinine > 2 mg/dl), or metabolic disorders
• secondary malignancy (except for curative treated basal cell carcinoma or cervical cancer)