OP0003 Single arm, multicentre, phase 2 study of clofarabine in Chinese paediatric patients with refractory or relapsed acute lymphoblastic leukaemia

Abstract

<h3>Background</h3> A phase 2 study was done to evaluate the safety and efficacy of clofarabine in paediatric patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) in China. <h3>Methods</h3> Patients aged 1–21years with histologically confirmed, relapsed or refractory ALL were eligible. Clofarabine was administered intravenously for 5days at 52mg/m² per day during induction and consolidation. The primary endpoint was overall remission rate (ORR; complete remission [CR] plus CR with incomplete counts [CRi]). Blood samples were collected for pharmacokinetic analysis. <h3>Findings</h3> A total of 44 patients were enrolled, of whom 43 were evaluable for response. The median age was 13years (range 5–22years), and the majority were B cell-ALL (75%, 33/44). The ORR was 44.2% (19/43), including two CR and 17 CRi. 39 patients had progressive disease at cut-off time; the overall median remission duration was 2.9months, and 3.4months for patients achieved CR or CRi. Subgroup analysis showed that efficacy differed significantly by age and phenotype of the cell (age <14years versus age ⩾14years: 60.9% versus 25%, <i>p</i>=0.0308; B-cell ALL versus T-cell ALL: 57.6% versus 0, <i>p</i>=0.002). The most common (⩾10%) adverse reactions (ADRs) were haematological toxicity, gastrointestinal reaction, and abnormal liver function, and the most common grade 3 or 4 non-haematological ADR was ALT elevation (13.6%). PK analysis showed that after multiple administrations the mean elimination half-life of clofarabine was 6.43h, and the Tmax was around 2h. The mean Cmax and exposure to clofarabine over the dosing period (AUC 0–24) were 581μg/L and 2602.56μg/L, respectively. <h3>Interpretation</h3> Single-agent clofarabine treatment is effective in Chinese paediatric patients with multiple relapsed or refractory ALL, with an acceptable safety profile.