UMIN-CTR Clinical Trial

Public title

Transhepatic arterial administration of G-CSF mobilized autologous peripheral blood CD34 positive cells in patients with hepatitis C virus-related liver cirrhosis

Acronym

Transhepatic arterial administration of G-CSF mobilized autologous peripheral blood CD34 positive cells in patients with hepatitis C virus-related decompensated liver cirrhosis

Scientific Title

Transhepatic arterial administration of G-CSF mobilized autologous peripheral blood CD34 positive cells in patients with hepatitis C virus-related liver cirrhosis

Scientific Title:Acronym

Transhepatic arterial administration of G-CSF mobilized autologous peripheral blood CD34 positive cells in patients with hepatitis C virus-related decompensated liver cirrhosis

Region

Japan

Condition

Decompensated liver cirrhosis (Hepatitis C virus-related)

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective is to examine the safety and efficacy of transhepatic administration of autologous G-CSF mobilized peripheral blood CD34 positive cells compared with standard medical therapy in patients with hepatitis C virus-related liver cirrhosis

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

Non-exacerbation rate of Child-Pugh score at 24 weeks after treatment

Key secondary outcomes

1) Child-Pugh Score
2) MELD Score
3) Ascites by abdominal ultrasonography and abdominal CT
4) Serum albumin, total protein, total bilirubin value and PT-INR
5) Serum hyaluronic acid and type-IV collagen
6) QOL evaluation by SF-36v2
7) Portal blood flow and velocity by abdominal ultrasonography
8) Death due to liver cirrhosis and all deaths
9) Onset of hepatocellular carcinoma
10) Performance and bugs of magnetic cell separation device

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Maneuver

Interventions/Control_1

G-CSF administration(5 days), Apheresis, Transhepatic arterial administration of CD34 positive cells

Interventions/Control_2

Standard medical therapy

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Patients with hepatitis C virus-related liver cirrhosis
2) Patients eligible for this study include those with hepatitis C virus-related decompensated liver cirrhosis with a Child-Pugh Score greater than or equal to 7 points in whom further improvement with current standard medical treatment is not expected at two points more than 90 days apart
3) Patients who aged 20 to 80 years
4) Patient who can give written informed consent themselves

Key exclusion criteria

1) Patients with HCV-related liver cirrhosis or cryptogenic liver cirrhosis
2) Patients who are positive for HBs-Ag, HIV-Ab, HTLV1-Ab, serological test for syphilis and HBc-Ab (CLIA method >10.00 S/CO)
3) Patients with alcoholic drinkers, Patients with a Child-Pugh Score less than or equal to 6 points in whom further improvement with abstinence for more than 6 months.
4) Patients complicated of malignant tumor or patients with a history of malignant tumor within 5 years (However, for patients with a history of intraepithelial carcinoma [e.g., colon mucosal cancer] and hepatocellular carcinoma, which are negative for AFP and PIVKA-II, is not excluded)
5) Total bilirubin> 5.0 mg/dL
6) Prothrombin time less than 30%
7) Serum creatinine> 2.0 mg/dL
8) Hemoglobin less than 8 g/dL
9) Platelet less than 20,000 / uL
10) Patients who have splenomegaly with longitudinal spleen diameter more than 15 cm by abdominal CT
11) Patients who have gastrointestinal bleeding or patients who may cause bleeding in the gastrointestinal tract
12) Patients with portal vein thrombosis
13) Patients currently suffering from or having a history of interstitial pneumonia
14) Patients with hematological disease (leukemia, myeloproliferative disease, myelodysplastic syndrome or sickle cell anemia)
15) Patients with autoimmune disease
16) Patients with less than 3 months since last episode of unstable angina, myocardial/cerebral infarction, Patients with less than 3 months since coronary artery/carotid artery/intracranial artery stenting
17) Patients with proliferative diabetic retinopathy
18) Patients with a history of severe allergic reactions or side effects to G-CSF, apheresis, or a contrast agents
19) Pregnant women, lactating women, patients who may be pregnant, female patients planning pregnancy during the study period
20) Any other reason that the Clinical Supervision or Clinical Researchers may have for considering a case unsuitable for the study

Target sample size

24

Name of lead principal investigator

1st name	Takuji
Middle name
Last name	Torimura

Organization

Kurume University School of Medicine

Division name

Division of Gastroenterology, Department of Medicine

Zip code

8300011

Address

67 Asahi-machi, Kurume, Fukuoka, Japan

TEL

0942-31-7561

Email

tori@med.kurume-u.ac.jp

Name of contact person

1st name	Toru
Middle name
Last name	Nakamura

Organization

Kurume University School of Medicine

Division name

Division of Gastroenterology, Department of Medicine

Zip code

8300011

Address

67 Asahi-machi, Kurume, Fukuoka, Japan

TEL

0942-31-7561

Homepage URL

Email

ntoru@med.kurume-u.ac.jp

Institute

Kurume University School of Medicine

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Shonan Kamakura General Hospital Certified Committee for Regenerative Medicine

Address

1370-1, Okamoto, Kamakura-shi, Kanagawa, Japan

Tel

03-3263-4801

Email

rm_committee2@shonankamakura.or.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

関西医科大学附属病院(大阪府)
兵庫医科大学病院（兵庫県）
湘南鎌倉総合病院（神奈川県）

Date of disclosure of the study information

2017

Year

09

Month

20

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTb070190052

Publication of results

Unpublished

URL related to results and publications

https://jrct.niph.go.jp/latest-detail/jRCTb070190052

Number of participants that the trial has enrolled

14

Results

The primary endpoint, the non-progression rate of Child-Pugh (CP) score at 24 weeks at 24 weeks after enrollment, was 90% in the cell transplant group and 100% in the standard treatment group, with no significant differences between groups.

Results date posted

2024

Year

03

Month

07

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The CD34+ cell group included 7 men and 3 women with a mean age of 62.8 +- 9.1 years, while the SOC group included 1 man and 3 women with a mean age of 70.8 +- 7.8 years. The CP score, which reflects the patients liver functional reserve, was 8.0 +- 1.2 points in the CD34+ cell group (9 patients in CP-B and 1 patient in CP-C) and 8.0 +- 1.4 points in the SOC group (3 patients in CP-B and 1 patient in CP-C). With regard to HCV elimination prior to enrollment, there were 2 non-SVR (HCV-RNA positive) patients and 8 SVR (HCV-RNA negative) patients in the CD34+ cell group, while there were 2 non-SVR patients and 2 SVR patients in the SOC group.

Participant flow

After written consent was obtained from 19 patients, a pre-enrollment examination was conducted, and 14 patients were enrolled after excluding those who were ineligible patients. Fourteen patients (10 in the CD34+ cell group and 4 in the SOC group) started treatment, all of whom completed the study period up to 52 weeks after enrollment.

Adverse events

Three serious adverse events occurred in the cell transplant group and one in the standard treatment group. There were no deaths due to cirrhosis, no all-cause mortality, and no occurrence of hepatocellular carcinoma in all patients.

Outcome measures

Primary endpoint: 1) Non-exacerbation rate of Child-Pugh score at 24 weeks after treatment, 2)Safety for protocol treatment (severity, severity and frequency of adverse events)
Secondary endpoint: 1) Child-Pugh Score, 2) MELD Score, 3) Ascites by abdominal ultrasonography and abdominal CT, 4) Serum albumin, total protein, total bilirubin value and PT-INR, 5) Serum hyaluronic acid and type-IV collagen, 6) QOL evaluation by SF-36v2, 7) Portal blood flow and velocity by abdominal ultrasonography, 8) Death due to liver cirrhosis and all deaths, 9) Onset of hepatocellular carcinoma, 10) Performance and bugs of magnetic cell separation device

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2017

Year

08

Month

22

Day

Date of IRB

2017

Year

03

Month

06

Day

Anticipated trial start date

2017

Year

09

Month

20

Day

Last follow-up date

2022

Year

11

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

09

Month

01

Day

Last modified on

2024

Year

03

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033137