Deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation: multicenter phase I study (KSGCT1302)
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The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22–68). Median time from HCT to deferasirox administration was 9 months (range 6–84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient.
KeywordsIron overload Deferasirox Post transplantation Optimal dose
We would like to thank all of the members of KSGCT, the data center, and the Safety and Efficacy Committee.
TT is the primary investigator and designed the protocol, managed the clinical trial, and wrote the manuscript. JK, SMachida, MTanaka, and MTakeuchi contributed to the protocol design and patient enrollment. TS, YN, SK, TM, and EY contributed to case registration. SMorita contributed to biomedical statistics. YK and HK contributed to study design and management. SO supervised the study.
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Conflict of interest
All authors except the two below have no conflict of interest to declare: Yuho Najima: personal financial interest on speakers’ bureaus from Novartis; Satoshi Morita: personal financial interest on speakers’ bureaus from Novartis.