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Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukemia : a randomized phase 3 trial

Chronic lymphocytic leukaemia (CLL) is an incurable and chronic disorder, with worsening prognosis for patients as their disease progresses. We compared the effi cacy and safety of the combination of fl udarabine and alemtuzumab with fl udarabine monotherapy in previously treated patients with relapsed or refractory CLL. Patients (aged ≥18 years) with CLL Binet stage A, B, or C or Rai stages I–IV were randomly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment (fl udarabine 30 mg/m² per day and alemtuzumab 30 mg per day on days 1–3) or monotherapy (fl udarabine 25 mg/m² on days 1–5) by use of an interactive voice response system. Both regimens were given intravenously for a maximum of six 28-day cycles. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00086580. Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fl udarabine monotherapy (n=167 ; median 23·7 months [95% CI 19·2–28·4] vs 16·5 months [12·5–21·2] ; hazard ratio 0·61 [95% CI 0·47–0·80] ; p=0·0003) and overall survival (median not reached vs 52·9 months [40·9–not reached] ; 0·65 [0·45–0·94] ; p=0·021) compared with fl udarabine alone. All-cause adverse events occurred in 161 (98%) of 164 patients in the combination treatment group and 149 (90%) of 165 in the fl udarabine alone group. Patients in the fl udarabine plus alemtuzumab group had more cytomegalovirus events (23 [14%] vs one [<1%]) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions (102 [62%] vs 22 [13%]). Grade 3 or 4 toxicities in the combination treatment and monotherapy groups were leucopenia (121 [74%] of 164 vs 55 [34%] of 164), lymphopenia (149 [94%] of 158 vs 53 [33%] of 161), neutropenia (93 [59%] of 157 vs 110 [68%] of 161), thrombocytopenia (18 [11%] of 164 vs 27 [17%] of 163), and anaemia (14 [9%] of 163 vs 28 [17%] of 164). The incidence of serious adverse events was higher in the combination treatment group (54 [33%] of 164 vs 41 [25%] of 165) ; deaths due to adverse events were similar between the two groups (ten [6%] vs 12 [7%]). The combination of fl udarabine and alemtuzumab is another treatment option for patients with previously treated CLL.

chronic lymphocytic leukemia fludarabine alemtuzumab trial

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