Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial

Introduction Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for...

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Main Authors: Hiroki Nishikawa, Shunsuke Ohnishi, Hiroshi Hayashi, Rika Okamoto, Kenichi Yamahara, Toshiyuki Isoe, Norihiro Sato, Akiko Hamada, Toshihiro Soma, Masaya Okada, Satoshi Yoshihara, Kyoko Yoshihara, Kazuhiro Ikegame, Hiroya Tamaki, Katsuji Kaida, Takayuki Inoue, Yuko Ohsugi, Hiroaki Iijima, Daigo Hashimoto, Takanori Teshima, Hiroyasu Ogawa, Yoshihiro Fujimori
Format: Article
Language:English
Published: BMJ Publishing Group 2019-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/7/e026403.full
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author Hiroki Nishikawa
Shunsuke Ohnishi
Hiroshi Hayashi
Rika Okamoto
Kenichi Yamahara
Toshiyuki Isoe
Norihiro Sato
Akiko Hamada
Toshihiro Soma
Masaya Okada
Satoshi Yoshihara
Kyoko Yoshihara
Kazuhiro Ikegame
Hiroya Tamaki
Katsuji Kaida
Takayuki Inoue
Yuko Ohsugi
Hiroaki Iijima
Daigo Hashimoto
Takanori Teshima
Hiroyasu Ogawa
Yoshihiro Fujimori
author_facet Hiroki Nishikawa
Shunsuke Ohnishi
Hiroshi Hayashi
Rika Okamoto
Kenichi Yamahara
Toshiyuki Isoe
Norihiro Sato
Akiko Hamada
Toshihiro Soma
Masaya Okada
Satoshi Yoshihara
Kyoko Yoshihara
Kazuhiro Ikegame
Hiroya Tamaki
Katsuji Kaida
Takayuki Inoue
Yuko Ohsugi
Hiroaki Iijima
Daigo Hashimoto
Takanori Teshima
Hiroyasu Ogawa
Yoshihiro Fujimori
author_sort Hiroki Nishikawa
collection DOAJ
description Introduction Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD.Methods and analysis This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01.Ethics and dissemination The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal.Trial registration number UMIN000029945.
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spelling doaj-art-8de132ce9cea4e4a97376e463c1d1a5d2025-08-20T02:28:01ZengBMJ Publishing GroupBMJ Open2044-60552019-07-019710.1136/bmjopen-2018-026403Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trialHiroki Nishikawa0Shunsuke Ohnishi1Hiroshi Hayashi2Rika Okamoto3Kenichi Yamahara4Toshiyuki Isoe5Norihiro Sato6Akiko Hamada7Toshihiro Soma8Masaya Okada9Satoshi Yoshihara10Kyoko Yoshihara11Kazuhiro Ikegame12Hiroya Tamaki13Katsuji Kaida14Takayuki Inoue15Yuko Ohsugi16Hiroaki Iijima17Daigo Hashimoto18Takanori Teshima19Hiroyasu Ogawa20Yoshihiro Fujimori214 Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan7 Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan5 Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan4 Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan1 Laboratory of Medical Innovation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, JapanClinical Research and Medical Innovation Center, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, JapanClinical Research and Medical Innovation Center, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan1 Laboratory of Medical Innovation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan2 Center for Transfusion Medicine and Cellular Therapy, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan2 Center for Transfusion Medicine and Cellular Therapy, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan2 Center for Transfusion Medicine and Cellular Therapy, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan5 Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan8 Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan8 Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan3 Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan1 Laboratory of Medical Innovation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, JapanIntroduction Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD.Methods and analysis This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01.Ethics and dissemination The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal.Trial registration number UMIN000029945.https://bmjopen.bmj.com/content/9/7/e026403.full
spellingShingle Hiroki Nishikawa
Shunsuke Ohnishi
Hiroshi Hayashi
Rika Okamoto
Kenichi Yamahara
Toshiyuki Isoe
Norihiro Sato
Akiko Hamada
Toshihiro Soma
Masaya Okada
Satoshi Yoshihara
Kyoko Yoshihara
Kazuhiro Ikegame
Hiroya Tamaki
Katsuji Kaida
Takayuki Inoue
Yuko Ohsugi
Hiroaki Iijima
Daigo Hashimoto
Takanori Teshima
Hiroyasu Ogawa
Yoshihiro Fujimori
Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
BMJ Open
title Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
title_full Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
title_fullStr Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
title_full_unstemmed Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
title_short Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial
title_sort safety and efficacy of amnion derived mesenchymal stem cells am01 in patients with steroid refractory acute graft versus host disease after allogeneic haematopoietic stem cell transplantation a study protocol for a phase i ii japanese trial
url https://bmjopen.bmj.com/content/9/7/e026403.full
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