Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 23;14(6):e084159.
doi: 10.1136/bmjopen-2024-084159.

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

Rintaro Ono  1 , Kenichi Sakamoto  2   3 , Ko Kudo  4 , Aki Sato  5 , Kazuko Kudo  6 , Hisanori Fujino  7 , Yuta Kawahara  8 , Hiroya Hashimoto  9 , Takehiko Doi  10 , Ryu Yanagisawa  11 , Toyotaka Kawamata  5   12 , Osamu Miyazaki  13 , Atsuko Nakazawa  14 , Yasunori Ota  15 , Hirokazu Kanegane  16 , Yozo Nakazawa  2 , Keizo Horibe  9 , Akiko M Saito  9 , Atsushi Manabe  17 , Kensuke Usuki  18 , Hitoshi Kiyoi  19 , Akira Morimoto  8   20 , Arinobu Tojo  21 , Yoko Shioda  22
Affiliations

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

Rintaro Ono et al. BMJ Open. .

Abstract

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.

Keywords: CHEMOTHERAPY; Clinical trials; HAEMATOLOGY.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Treatment outlines of (A) the multisystem and (B) multifocal bone LCH. Ara-C, cytarabine; DEX, dexamethasone; IT, intrathecal administration of cytarabine plus prednisolone; LCH, Langerhans cell histiocytosis; MTX, methotrexate; PSL, prednisolone; VBL, vinblastine; 6-MP, 6-mercaptopurine; VCR, vincristine; ZOL, zoledronate acid.
See this image and copyright information in PMC

References

    1. Gadner H, Grois N, Arico M, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001;138:728–34. doi: 10.1067/mpd.2001.111331. - DOI - PubMed
    1. Gadner H, Grois N, Pötschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111:2556–62. doi: 10.1182/blood-2007-08-106211. - DOI - PubMed
    1. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121:5006–14. doi: 10.1182/blood-2012-09-455774. - DOI - PubMed
    1. Morimoto A, Ikushima S, Kinugawa N, et al. Improved outcome in the treatment of pediatric multifocal Langerhans cell histiocytosis: results from the Japan Langerhans cell Histiocytosis study Group-96 protocol study. Cancer. 2006;107:613–9. doi: 10.1002/cncr.21985. - DOI - PubMed
    1. Morimoto A, Shioda Y, Imamura T, et al. Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study. Int J Hematol. 2016;104:99–109. doi: 10.1007/s12185-016-1993-3. - DOI - PubMed

Publication types

LinkOut - more resources