Increased remissions from one course for intermediate‐dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population‐based phase II study

Cladribine has single‐drug activity in acute myeloid leukaemia (AML), and may enhance the formation of the active metabolite (ara‐CTP) of cytosine arabinoside (ara‐C). To evaluate the feasibility of adding intermittent cladribine to intermediate‐dose ara‐C (1 g/m2/2 h) b.i.d. for 4 d with idarubicin (CCI), we performed a 2:1 randomized phase II trial in AML patients aged over 60 years. Primary endpoints were time to recovery from cytopenia and need for supportive care following the first course. Sixty‐three patients (median 71 years, range 60–84 years) were included, constituting 72% of all eligible patients. Toxicity was limited, with no differences between the treatment arms. The early toxic death rate was 11%. The median time to recovery from neutropenia and thrombocytopenia was 22 and 17 d from the start of course no. 1, respectively, and the requirement for platelet and red cell transfusions was four and eight units respectively. Patients had a median of 8 d with fever over 38°C, and 17 d with intravenous antibiotic treatment. The overall complete remission (CR) rate was 62%, with 51% CR from one course of CCI in comparison with 35% for the two‐drug therapy (P = 0·014). The median survival with a 2‐year follow‐up was 14 months, and the 2‐year survival was over 30%, with no differences between the treatment arms. Considering the median age and our population‐based approach, the overall results are encouraging.