Cargando…

Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)

BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of sali...

Descripción completa

Detalles Bibliográficos
Autores principales: Sumita, Yoshinori, Iwamoto, Naoki, Seki, Makoto, Yoshida, Takako, Honma, Ryo, Iwatake, Mayumi, Ohba, Seigo, Takashi, I., Hotokezaka, Yuka, Harada, Hiroshi, Kuroshima, Shinichiro, Nagai, Kazuhiro, Asahara, Takayuki, Atsushi Kawakam, I, Asahina, Izumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328916/
https://www.ncbi.nlm.nih.gov/pubmed/32590759
http://dx.doi.org/10.1097/MD.0000000000020788
_version_ 1783552814258061312
author Sumita, Yoshinori
Iwamoto, Naoki
Seki, Makoto
Yoshida, Takako
Honma, Ryo
Iwatake, Mayumi
Ohba, Seigo
Takashi, I.
Hotokezaka, Yuka
Harada, Hiroshi
Kuroshima, Shinichiro
Nagai, Kazuhiro
Asahara, Takayuki
Atsushi Kawakam, I
Asahina, Izumi
author_facet Sumita, Yoshinori
Iwamoto, Naoki
Seki, Makoto
Yoshida, Takako
Honma, Ryo
Iwatake, Mayumi
Ohba, Seigo
Takashi, I.
Hotokezaka, Yuka
Harada, Hiroshi
Kuroshima, Shinichiro
Nagai, Kazuhiro
Asahara, Takayuki
Atsushi Kawakam, I
Asahina, Izumi
author_sort Sumita, Yoshinori
collection PubMed
description BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057.
format Online
Article
Text
id pubmed-7328916
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Wolters Kluwer Health
record_format MEDLINE/PubMed
spelling pubmed-73289162020-07-09 Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia) Sumita, Yoshinori Iwamoto, Naoki Seki, Makoto Yoshida, Takako Honma, Ryo Iwatake, Mayumi Ohba, Seigo Takashi, I. Hotokezaka, Yuka Harada, Hiroshi Kuroshima, Shinichiro Nagai, Kazuhiro Asahara, Takayuki Atsushi Kawakam, I Asahina, Izumi Medicine (Baltimore) 3700 BACKGROUND: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. METHODS/DESIGN: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. DISCUSSION: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials (http://jrct.niph.go.jp) as jRCTb070190057. Wolters Kluwer Health 2020-06-26 /pmc/articles/PMC7328916/ /pubmed/32590759 http://dx.doi.org/10.1097/MD.0000000000020788 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle 3700
Sumita, Yoshinori
Iwamoto, Naoki
Seki, Makoto
Yoshida, Takako
Honma, Ryo
Iwatake, Mayumi
Ohba, Seigo
Takashi, I.
Hotokezaka, Yuka
Harada, Hiroshi
Kuroshima, Shinichiro
Nagai, Kazuhiro
Asahara, Takayuki
Atsushi Kawakam, I
Asahina, Izumi
Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title_full Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title_fullStr Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title_full_unstemmed Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title_short Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
title_sort phase 1 clinical study of cell therapy with effective-mononuclear cells (e-mnc) for radiogenic xerostomia (first-in-human study) (fih study on e-mnc therapy for radiogenic xerostomia)
topic 3700
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328916/
https://www.ncbi.nlm.nih.gov/pubmed/32590759
http://dx.doi.org/10.1097/MD.0000000000020788
work_keys_str_mv AT sumitayoshinori phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT iwamotonaoki phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT sekimakoto phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT yoshidatakako phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT honmaryo phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT iwatakemayumi phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT ohbaseigo phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT takashii phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT hotokezakayuka phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT haradahiroshi phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT kuroshimashinichiro phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT nagaikazuhiro phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT asaharatakayuki phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT atsushikawakami phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia
AT asahinaizumi phase1clinicalstudyofcelltherapywitheffectivemononuclearcellsemncforradiogenicxerostomiafirstinhumanstudyfihstudyonemnctherapyforradiogenicxerostomia