Clofarabine was the latest new drug to be approved, in 2004, for relapsed or refractory acute lymphoblastic leukaemia (ALL). To investigate its value in the frontline treatment of ALL we applied clofarabine 5 × 40 mg/m(2) in combination with pegylated asparaginase (PEG-ASP) 1 × 2500 iu/m(2) in high risk ALL patients as a novel post-induction element in the German Co-operative Study Group for treatment of ALL (CoALL) trial 08-09. Newly diagnosed ALL patients, defined by a significant minimal residual disease (MRD) load at the end of induction (B-progenitor ALL at day 29 ≥ 10(-4) and T-ALL at day 43 ≥ 10(-3) ) were eligible for this phase II trial. All other patients received the standard treatment consisting of high-dose cytarabine (HIDAC) 4 × 3 g/m² in combination with Peg-ASP 2500 iu/m². Forty-two patients (39 B-progenitor; 3 T-ALL) fulfilled the criteria, were stratified and received the clofarabine/PEG-ASP treatment resulting in 24/39 (61%) MRD-negative B-progenitor patients compared to 18/39 (46%) after HIDAC/PEG-ASP in CoALL 07-03. Overall, the toxicity profile of clofarabine/PEG-ASP was similar to HIDAC/PEG-ASP without unexpected severe side effects. Clofarabine combined with PEG-ASP is safe and effective in the frontline treatment of ALL. A prospective, randomized trial is warranted to evaluate the antileukaemic efficacy of clofarabine versus HIDAC combined with PEG-ASP.
