UMIN-CTR Clinical Trial

Basic information
Public title	Phase I clinical trial with umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for treatment-resistant severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation
Acronym	Phase I clinical trial with umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for treatment-resistant severe acute graft-versus-host disease (GVHD)
Scientific Title	Phase I clinical trial with umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for treatment-resistant severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation
Scientific Title:Acronym	Phase I clinical trial with umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for treatment-resistant severe acute graft-versus-host disease (GVHD)
Region	Japan

Condition
Condition	First line treatment-resistant Grade II to IV acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	The aim of this study is to evaluate the safety and exploratory efficacy of umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for patients with first line treatment-resistant grade II to IV severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Safety: 1) Incidence of Dose Limited Toxicity (DLI) and determination of optical dose for phase II studies. 2) Evaluation of adverse events such as the rate of events, until 11 weeks after the last administration of IMSUT-CORD. 3) Statistical evaluation of laboratory tests until 11 weeks after the last administration of IMSUT-CORD.
Key secondary outcomes	Efficacy: 1) Overall response and change of stage/grading of organ damages by acute GVHD at 11 weeks after the last administration of IMSUT-CORD 2) Overall survival (OS)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Other
Interventions/Control_1	Intravenous of IMSUT-CORD with dose escalation by 3+3 design Cohort 1 dose:1x10^6cells /kg, Cohort 2 dose:2x10^6 cells /kg, Cohort -1 dose:5x10^5 cells /kg After safety confirmation at cohort 1, proceed to cohort 2. If two patients reveal DLT in at cohort 1, cohort -1 will be tested. One cycle is defined as twice a week administration, and standard treatment is 2 cycles of administration. Up to two cycles of administration (total four cycles) is allowed for patients with no significant adverse effects and Partial response (PR) or Mixed response (MR).
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	70 years-old >=
Gender	Male and Female
Key inclusion criteria	Inclusion criteria: 1. Patients with grade II to IV acute GVHD. Pathological diagnosis is required, if possible. 2. Patients resistant to standard therapy with glucocorticoid. 3. Patients Aged 20 to 70 years at the time of consent 4. Patients who can give their consent by the written form.
Key exclusion criteria	Exclusion criteria: 1. Patients NOT treated with standard first-line treatment with glucocorticoid for acute GVHD (except for prevention therapy for acute GVHD). 2. Patients treated with hematopoietic stem cell transplantation for hematopoietic malignancies under no remission, except for myelodysplastic syndrome with or without leukemic transition and myeloproliferative diseases. 3. Patients with following severe complications within 14 days before registration. a) Cardiac function: Ejection fraction <40% b) Pulmonary function: SpO2 < 90% or SpO2 < 95% under oxygen inhalation. c) Renal function: serum creatinine -> 2 times of upper limit of institutional normal range (ULN). d) Liver function: serum total bilirubin ->3 times of ULN, AST/ALT -> 5 times of ULN. 4. Pregnant/possible pregnant and nursing woman. Patients refuse to contraception. 5. Patients positive for HIV antibodies, HTLV-I antibodies, HBs antigen, and HCV antibodies. 6. Therapy resistant hypertension 7. Patient who have allergy against reagents used for processing, such as amphotericin B, gentamicin. Patients treated as emergency for adverse reaction of DMSO. 8.Investigators decision as not eligible.
Target sample size	6

Research contact person
Name of lead principal investigator	1st name Middle name Last name Arinobu Tojo
Organization	The Institute of Medical Science, The University of Tokyo
Division name	Department of Hematology/Oncology, IMSUT Hospital
Zip code
Address	4-6-1, Shirokanedai, Minato-ku, Tokyo
TEL	03-3443-8111
Email	dctsm@ims.u-tokyo.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Center for Translational Research
Organization	The Institute of Medical Science, The University of Tokyo
Division name	Center for Translational Research
Zip code
Address	4-6-1, Shirokanedai, Minato-ku, Tokyo
TEL	03-5449-5462
Homepage URL
Email	dctsm@ims.u-tokyo.ac.jp

Sponsor
Institute	The Institute of Medical Science, The University of Tokyo
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	東京大学医科学研究所附属病院(東京都) 国家公務員共済組合連合会虎の門病院（東京都） がん・感染症センター都立駒込病院（東京都）

Other administrative information
Date of disclosure of the study information	2018 Year 06 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 04 Month 12 Day
Date of IRB	2018 Year 02 Month 20 Day
Anticipated trial start date	2018 Year 06 Month 01 Day
Last follow-up date	2020 Year 06 Month 29 Day
Date of closure to data entry
Date trial data considered complete	2020 Year 09 Month 11 Day
Date analysis concluded	2021 Year 01 Month 25 Day

Other
Other related information

Management information
Registered date	2018 Year 05 Month 31 Day
Last modified on	2021 Year 06 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037403