Trial Outcomes & Findings for Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis (NCT NCT01503749)

Last Updated: 2014-12-19

Results Overview

No serious adverse event. Minor adverse events (not considered to be related to this study), as follows; Control: 6 events (ascites and pleural tapping, gum bleeding, ascties tapping x3, diarrhea) G-colony stimulating factor group: 6 events (percutaneous vertebroplasty, abdominal pain and nausea, hyperkalemia, ascties tapping, diarrhea, liver transplantation) Infusion of the mobilized peripheral blood mononucleated cells group: 1 event (hepatic encephalopathy)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

up to 6 months

Results posted on

2014-12-19

Participant Flow

Recruitment location: single medical center (Seoul National University Hospital) Recruitment period: between February 2012 and July 2013

Number of total enrolled pariticipants: 9 Number of screened participants: 14 Number of dropped participants: 5 (Withdraw consent:4, etc:1 due to development of hepatocellular carcinoma) Number of completed participants: 9

Participant milestones

Participant milestones
Measure	Control Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells .	G-colony Stimulating Factor G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.	Infusion of the Mobilized Peripheral Blood Mononucleated Cells G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Overall Study STARTED	3	3	3
Overall Study COMPLETED	3	3	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=3 Participants Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells .	G-colony Stimulating Factor n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.	Infusion of the Mobilized Peripheral Blood Mononucleated Cells n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Age, Continuous	57 years n=5 Participants	62 years n=7 Participants	63.3 years n=5 Participants	60.8 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Korea, Republic of	3 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	9 participants n=4 Participants

PRIMARY outcome

Timeframe: up to 6 months

Population: Nine patients who fulfilled the inclusion and exclusion criteria.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells .	G-colony Stimulating Factor n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.	Infusion of the Mobilized Peripheral Blood Mononucleated Cells n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Number of Participants With Severe Adverse Events	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: A total of 9 decompensated cirrhotic patients (5 men and 4 females, age range 45-71 years) grouped by randomization.

The efficacy (mean change in Child-Pugh score and Model For End-Stage Liver Disease score \[at weeks 24\]) of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell in cirrhotic patients. MELD Score = (0.957 \* ln(Serum Cr) + 0.378 \* ln(Serum Bilirubin) + 1.120 \* ln(INR) + 0.643 ) \* 10 (if hemodialysis, value for Creatinine is automatically set to 4.0) (minimum \<9: 1.9% mortality; maximum 40 or more: 71.3% mortality). Child-Pugh score = Bilirubin (mg/dl): \<2 (1 point),2-3 (2 points), \>3 (3 points) + Albumin (g/dl): \>3.5 (1 point),3.5-2.8 (2 points), \<2.8 (3 points) + PT prolongation (INR): \<4 seconds (\<1.7) (1 point), 4-6 seconds (1.7-2.3) (2 points),\>6 seconds (\>2.3) (3 points) + Ascites: Absent (1 point), Slight (2 points), Moderate (3 points) + Encephalopathy: Absent (1 point), Mild (I-II) (2 points), Severe (III-IV) (3 points) ; Class A: 5-6, Class B: 7-9, Class C: 10-15 (minimum 5, maximum 15; higher Child-Pugh score with worse prognosis)

Outcome measures

Outcome measures
Measure	Control n=3 Participants Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells .	G-colony Stimulating Factor n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.	Infusion of the Mobilized Peripheral Blood Mononucleated Cells n=3 Participants G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score Baseline Child-Pugh score	9 score Standard Deviation 1	10 score Standard Deviation 1	9 score Standard Deviation 1
Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score Child-Pugh score at 24 weeks	9.5 score Standard Deviation 2.5	10 score Standard Deviation 2	8.3 score Standard Deviation 1.1
Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score Baseline MELD score	15.9 score Standard Deviation 3.2	18.9 score Standard Deviation 2.2	14.4 score Standard Deviation 2.2
Mean Change in Child-Pugh Score and Model For End-Stage Liver Disease (MELD) Score MELD score at 24 weeks	15.5 score Standard Deviation 3.9	24.0 score Standard Deviation 3.9	14.7 score Standard Deviation 3.4

Adverse Events

Control

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

G-colony Stimulating Factor

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Infusion of the Mobilized Peripheral Blood Mononucleated Cells

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Control n=3 participants at risk Three patients with liver cirrhosis of this arm will not receive any intervention regarding to peripheral blood mononucleated cells .	G-colony Stimulating Factor n=3 participants at risk G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. G-colony stimulating factor: G-colony stimulating factor (5ug/kg/day)will be administered subcutaneously to three patients with liver cirrhosis of this arm.	Infusion of the Mobilized Peripheral Blood Mononucleated Cells n=3 participants at risk G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells . And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance. Infusion of the mobilized peripheral blood mononucleated cells: G-colony stimulating factor (5ug/kg/day)will be administered twice subcutaneously for 3 days to three patients with liver cirrhosis of this arm. On the day 4th, leukapheresis will be done to collect peripheral blood mononucleated cells. And then we are going to infuse the collected peripheral blood mononucleated cells of their own through the portal vein of each patients under ultrasonographic guidance.
Nervous system disorders hepatic encephalopathy	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Hepatobiliary disorders ascties tapping	66.7% 2/3 • Number of events 4 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Hepatobiliary disorders Liver transplantation	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Renal and urinary disorders hyperkalemia	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Musculoskeletal and connective tissue disorders percutaneous vertebroplasty	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Gastrointestinal disorders nausea	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Gastrointestinal disorders diarrhea	66.7% 2/3 • Number of events 2 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).
Blood and lymphatic system disorders gum bleeding	33.3% 1/3 • Number of events 1 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).	0.00% 0/3 • from the baseline till at week 24 No splenic rupture among the patients who received G-CSF mobilization during the study period (till at week 24). No bleeding or infection after portal administration of PBMCs during the study period (till at week 24).

Additional Information

Pf. Jung-Hwan Yoon

Seoul National University Hospital

Phone: 82-2-2072-2228

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place