Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes

Abstract

Purpose: This open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low- or intermediate-1-risk myelodysplastic syndrome (MDS).

Patients and methods: Patients received decitabine 20 mg/m(2) SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m(2) SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR: complete remission [CR], partial remission [PR], marrow CR [mCR], or hematologic improvement [HI]). Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death.

Results: Efficacy and safety populations were identical: schedule A, n = 43; schedule B, n = 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%).

Conclusion: In this phase II study, low-dose decitabine showed promising results in patients with low- or intermediate-1-risk MDS.

Trial registration: ClinicalTrials.gov NCT00619099.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Patient disposition.

Fig 2.

(A) Overall survival. Median was not reached. (B) Time to acute myeloid leukemia (AML) transformation or death. Median was not reached. (C) Median overall survival by myelodysplastic syndrome prognostic score category (n = 62). Note that three patients in the modified intent-to-treat population (n = 65) were excluded because they had missing bone marrow blast results and so could not be categorized. Median was not reached. KM, Kaplan-Meier. (*) Showing last data point.