Results of a Randomized, Open-Label, Phase IIIb Study of 2 Schedules of Decitabine in Higher-Risk Myelodysplastic Syndrome Patients

• Published in: Blood 2012-11, Vol.120 (21), p.3846-3846
• Main Authors: Wu, Depei, Du, Xin, Jin, Jie, Xiao, Zhijian, Shen, Zhixiang, Shao, Zonghong, Li, Xiao, Huang, Xiaojun, Liu, Ting, Yu, Li, Li, Jianyong, Chen, Baoan, He, Guangsheng, Cai, Zhen, Ruan, Changgeng
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.3846.3846

Abstract 3846 To evaluate the efficacy and safety of 3-day and 5-day treatment schedules of decitabine (nucleoside analogue) in Chinese patients with Myelodysplastic Syndrome (MDS). In this open-label, multi-center, phase 3b study, consenting men and women (n=132) above 18 years of age with de novo or secondary MDS fitting any of the recognized French-American-British classifications, with score on International Prognostic Scoring System (IPSS) ≥ 0.5 within 30 days before randomization, and having Eastern Cooperative Oncology Group performance (ECOG) status of 0–2, were enrolled. Patients were randomized (1:1) to either 3-day treatment schedule (15 mg/m2/day decitabine administered by continuous intravenous infusion within a 3-hour period, repeated every 8 hours for 3 consecutive days/cycle; cycles repeated every 6 weeks) or to 5-day treatment schedule (20 mg/m2 decitabine administered by a 1-hour infusion once-daily, on days 1 through 5/cycle; cycles repeated every 4 weeks), until minimum of 30 patients were included in the 3-day treatment group. All remaining patients were enrolled for the 5-day treatment. Patients were treated for ≥4 treatment cycles and for a maximum of 2 years, as long as the patient continued to benefit (absence of overt progression of disease or unacceptable toxicity). The primary efficacy endpoint was overall response rate (ORR) that included complete remission, bone marrow complete remission and partial remission, according to the International Working Group (IWG) 2006 response criteria. The secondary endpoints included hematological improvement, time to acute myeloid leukemia (AML) progression or death, and overall survival (OS). Safety and pharmacokinetics of decitabine were evaluated. Assuming a 10% dropout rate, with 132 enrolled patients, the study had 90% power at a 5% significance level to detect a >10% ORR. Thirty-four patients were included in the 3-day treatment group and 98 patients were included in the 5-day treatment group. Overall, 78 (59.5%) patients prematurely discontinued the study (16 [12.2%] patients discontinued due to disease progression). The demographic and baseline characteristics were comparable between the 2 treatment groups. In the overall population, the median age was 53.9 years (range: 18.5 – 84.0), 59% were men, all had de novo MDS, the mean (SD) time since diagnosis of MDS was 4.2 (9.38) months, 41.4% patients were IPSS Intermediate-1 (0.5–1.0), 43% were IPSS Intermediate −2 (1.5–2.0) and 15.6% wer