Phase II study in children and adults under 40 years with newly diagnosed Langerhans cell histiocytosis: protocol for an LCH-19-MSMFB clinical trial in Japan
Akiko M Saito,
Hiroya Hashimoto,
Takehiko Doi,
Arinobu Tojo,
Hirokazu Kanegane,
Hisanori Fujino,
Aki Sato,
Keizo Horibe,
Yuta Kawahara,
Yozo Nakazawa,
Atsuko Nakazawa,
Rintaro Ono,
Kenichi Sakamoto,
Ko Kudo,
Kazuko Kudo,
Ryu Yanagisawa,
Toyotaka Kawamata,
Osamu Miyazaki,
Yasunori Ota,
Atsushi Manabe,
Kensuke Usuki,
Hitoshi Kiyoi,
Akira Morimoto,
Yoko Shioda
Affiliations
Akiko M Saito
Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan
Hiroya Hashimoto
Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan
Takehiko Doi
Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
Arinobu Tojo
Institute of Innovation, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
Hirokazu Kanegane
Department of Child Health and Development, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
Hisanori Fujino
Department of Pediatrics, Osaka Red Cross Hospital, Osaka, Japan
Aki Sato
Department of Hematology and Oncology, The Institute of Medical Science Research Hospital, The University of Tokyo, Tokyo, Japan
Keizo Horibe
Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan
Yuta Kawahara
Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan
Yozo Nakazawa
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
Atsuko Nakazawa
Department of Clinical Research, Saitama Children’s Medical Center, Saitama, Japan
Rintaro Ono
Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan
Kenichi Sakamoto
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
Ko Kudo
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
Kazuko Kudo
Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan
Ryu Yanagisawa
Division of Blood Transfusion, Shinshu University Hospital, Matsumoto, Japan
Toyotaka Kawamata
Department of Hematology and Oncology, The Institute of Medical Science Research Hospital, The University of Tokyo, Tokyo, Japan
Osamu Miyazaki
Department of Radiology, National Center for Child Health and Development, Tokyo, Japan
Yasunori Ota
Department of Diagnostic Pathology, The Institute of Medical Science Research Hospital, The University of Tokyo, Tokyo, Japan
Atsushi Manabe
Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Kensuke Usuki
Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan
Hitoshi Kiyoi
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Akira Morimoto
Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan
Yoko Shioda
Children`s Cancer Center, National Center for Child Health and Development, Tokyo, Japan
Introduction Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.Methods and analysis This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.Ethics and dissemination This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.Trial registration number jRCTs041210027.
