9521 Background: This phase I study evaluated the tolerability of clofarabine with liposomal daunorubicin in childhood refractory/relapsed AML. Clofarabine is a purine nucleoside analogue, approved by EMA and FDA in relapsed/refractory childhood ALL but its application in childhood AML is unproven. AML17, the UK front line study for AML is investigating the efficacy of daunorubicin with clofarabine vs a standard chemotherapy block for a high-risk subgroup. Patients under 16 yrs are excluded, as safety data and a recommended dose for a clofarabine/anthracycline combination are not available. The primary objective is to establish the MTD of clofarabine combined with liposomal daunorubicin. Liposomal daunorubicin is used to minimize potential cardiotoxicity in eligible patients with previous exposure to significant doses of anthracyclines. The study characterizes the safety and tolerability of the combination and the overall response rate and the number of patients that subsequently undergo stem cell transplant (SCT). Eligibility criteria include; AML relapse within 12 mths of initial diagnosis,AML refractory to induction therapy or 2nd/subsequent relapse, Age; 6 mths to <18 yrs. previous daunorubicin/ equivalent exposure < 450mg/m2. Patients with extramedullary leukemia and CNS involvement were excluded.
METHODS
Using a standard 3+3 dose escalation design, patients recieved iv clofarabine days 1-5, and iv liposomal daunorubicin 60mg/m2 days 1,3 and 5. The starting dose of clofarabine was 30mg/m2 escalating to 40mg/m2. The primary endpoint was the appearance of dose limiting (DLTs) and defining the MTD.
RESULTS
9 patients were recruited. The most common SAE was neutropenic fever. No DLTs were observed. 3/9 patients had a complete response and proceeded to SCT. The 40mg/m2 cohort is being extended to accrue more efficacy data.
CONCLUSIONS
The combination of clofarabine with liposomal daunorubicin was well tolerated in heavily pre-treated pediatric AML patients. The MTD was not reached but promising responses were observed at both dose levels of clofarabine.