Efficacy and safety of risk-stratified chemotherapy with azacitidine for children with myeloid leukaemia with Down syndrome: protocol for a multicentre phase II trial (JCCG AML-D24)
Year: 2026
Type: article
Study design: Study Protocol
Abstract: INTRODUCTION: The prognosis of myeloid leukaemia associated with Down syndrome (ML-DS) is excellent with reduced-intensity chemotherapy; however, that of refractory or relapsed ML-DS remains dismal. These contrasting outcomes highlight the importance of risk-stratified therapy, based on reliable prognostic factors, to prevent treatment-related mortality and relapse. In addition, novel therapeutic strategies capable of overcoming the poor prognosis of high-risk patients are eagerly anticipated. Based on the results of molecular analyses, in vitro functional assays and anecdotal case reports, azacitidine (AZA), a hypomethylating agent, is a promising candidate for novel therapeutic strategies for high-risk ML-DS. METHODS AND ANALYSIS: mutation who achieve morphological complete remission and are negative for flow cytometric measurable residual disease at the end of induction will be classified as the low-risk (LR) group and receive less intensive chemotherapy. The other participants, stratified into the non-LR group, will be treated with AZA-combined chemotherapy. The objective of this trial is to evaluate the efficacy and safety of AZA-combined chemotherapy in children with non-LR ML-DS. The primary endpoint is the 3-year event-free survival in the non-LR group. The planned enrolment is 145 patients, including 47 non-LR patients. The study period consists of a 7-year accrual period (including an enrolment suspension period for interim analysis) followed by a 3-year follow-up period for a total duration of 10 years. ETHICS AND DISSEMINATION: This study was approved by the National Hospital Organization Review Board for Clinical Trials (Nagoya, Japan) on 12 May 2025 and was registered in the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/latest-detail/jRCTs041250031). Written informed consent will be obtained from all patients and/or their guardians. The results of this study will be disseminated through publication in peer-reviewed journals and presentation at national and international scientific conferences. TRIAL REGISTRATION NUMBER: jRCTs041250031.
Source: BMJ Open
Authors: Kentaro Nakashima, Daisuke Hasegawa, Jun Matsubayashi, Shiro Tanaka, Asahito Hama, Genki Yamato, Shota Kato, Mamoru Honda, Kozo Nagai, Hironori Goto, Shin-Ichi Tsujimoto, Takao Deguchi, Kaori Niwa, Hidefumi Hiramatsu, Kiminori Terui, Tsutomu Toki, Kenichi Yoshida, Tomoko Kawai, Akiko M Saito, Hiroshi Moritake, Takashi Taga, Yasuhiro Okamoto, Katsuyoshi Koh, Daisuke Tomizawa
Institutions: Kyushu University, St. Luke's International Hospital, Shiga University of Medical Science, Kyushu University Hospital, Gunma University, The University of Tokyo, Saitama Children's Medical Center, Ehime Prefectural Central Hospital, Oita University, Yokohama City University, National Center For Child Health and Development, Mie University, Kyoto University, Kindai University Sakai Hospital, Kindai University, Hirosaki University, National Cancer Center Research Institute, National Research Institute for Child Health and Development, Nagoya Medical Center, University of Miyazaki, Kagoshima University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,839
OpenAlex ID: W7214986798