Clofarabine in combination with pegylated asparaginase in the frontline treatment of childhood acute lymphoblastic leukaemia: a feasibility report from the Co ALL 08-09 trial.

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/m² in combination with pegylated asparaginase ( PEG- ASP) 1 × 2500 iu/m² in high risk ALL patients as a novel post-induction element in the German Co-operative Study Group for treatment of ALL (Co ALL) 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 Co ALL 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. [ABSTRACT FROM AUTHOR]