Intrahepatic Reinfusion of CD133+ Stem Cells in Cirrhotic Patients

NCT01025622 | Unknown Phase 1 DMC

• 1 other identifier: 2009-011783-10
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

OBJECTIVE(S): Primary: To assess the safety of the intrahepatic reinfusion of increasing numbers of autologous highly purified CD133+ stem cells (SCs) to patients with end-stage liver disease. Safety will be evaluated as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory value following reinfusion of SCs. Secondary: To assess the feasibility of the immunomagnetic selection of autologous CD133+ cells collected with leukapheresis from the peripheral blood (PB) of patients with end-stage liver disease, previously mobilized with G-CSF. To assess the effects of the intrahepatic reinfusion of highly purified CD133+ cells on residual hepatic function of the patients. STUDY DESIGN: Twelve patients will be enrolled. At first, G-CSF at 7.5µg/Kg/b.i.d. will be administered subcutaneously (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Harvest of bone marrow (BM)-derived PBSC will begin on day + 4 only if the concentration of CD133+ cells is \> 8/uL and will be continued until the collection of the target cell dose: 0.5 x 106 CD133+ cells/Kg for the first 2 cohorts of patients; 1 x 106 CD133+ cells/Kg for cohort 3 and 2 x 106 CD133+ cells/Kg for cohort 4 (see below for definitions). PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads and CliniMacs device will be used for the positive selection of CD133+ cells under good manufacturing practice (GMP) conditions. Cryopreservation and storage in liquid nitrogen will be performed according to standard procedures. At least 4 weeks after SC mobilization and collection, up to 40 mL of single cell suspension of highly purified autologous CD133+ cells, obtained after rapid thawing, will be infused through the hepatic artery by transfemoral or transbrachial arteriography. Infusion time will be lower than 15ml/min to avoid thrombi formation. The entire procedure will be performed under anesthesiological control. According to modified Fibonacci's increment rule, highly purified G-CSF-mobilized CD133+ cells will be administered to patients starting from 5x104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1x106/kg. G-CSF at 5µg/Kg/day will be administered sc for 3 days after the reinfusion of SCs (day 0 to day +2).

Conditions

Liver Cirrhosis

Keywords

Stem Cells; Liver Cirrhosis; Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Safety: Incidence of adverse events (graded according to WHO). Incidence of clinically significant abnormal laboratory values following reinfusion of highly purified CD133+ cells.

  1 year

Secondary Outcomes (1)

• Effects of the intrahepatic reinfusion of highly purified CD133+ SCs on residual hepatic function of the patients: Child-Turcotte-Pugh and MELD score.

  1 year

Interventions

autologous highly purified CD133+ stem cells (SCs) BIOLOGICAL

Intrahepatic reinfusion in cirrhotic patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age \>18 years
• Karnofsky score \>70% or WHO \<1
• Adequate renal (serum creatinine \< 2 mg/dl) and pulmonary (Sat O2 \>96%) function
• Diagnosis of advanced, end-stage liver disease defined by a Mayo Model for End Stage Liver Disease (MELD) score between 17 and 25. Patients with the following liver disease etiologies will be enrolled in the study: chronic viral hepatitis B, chronic viral hepatitis C, chronic viral hepatitis D, alcoholic cirrhosis (without alcohol active consumption), primary sclerosing cholangitis, primary biliary cirrhosis, Wilson's disease, genetic hemochromatosis or iron over-load cirrhosis, cirrhosis due to non alcoholic steato-hepatitis.
• Eligibility for orthotopic liver transplantation (OLT) is not a contraindication to enter in the clinical study. Patients in waiting list for OLT transplantation will not be withdrawn and will be transplanted as soon as a suitable donor will become available.Their MELD score will remain that recorded prior SCs infusion in case of improvement following the experimental procedure.
• The presence of cirrhosis related symptoms, like ascites, peripheral edema, recurrent gastrointestinal tract bleeding, recurrent encephalopathy do not represent major contraindications to be enrolled into the study.
• The patients may be considered eligible when clinically stable.

You may not qualify if:

• HIV positivity
• Pregnant or nursing females
• Current uncontrolled infection
• Intercurrent organ damage
• Diagnosis of hepatocarcinoma
• Complete portal thrombosis
• Severe impairment of coagulative function (PT\< 30%, INR\>2.5, Platelets \< 40x109/L) that would contraindicate arteriography
• Grade IV splenomegaly
• Budd-Chiari Syndrome with sovrahepatic vein thrombosis and cirrhosis of unknown origin will not be included in the study

Sponsors & Collaborators

• University of Bologna: lead

Study Sites (2)

Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi,

Bologna, 40138, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

Related Links

• Local ethics committee

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roberto M Lemoli, MD

  University of Bologna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto M Lemoli, MD

CONTACT

+390516363680; roberto.lemoli@unibo.it

Pietro Andreone, MD

CONTACT

+390516363817; pietro.andreone@unibo.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 3, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2012
• Last Updated: October 29, 2010

Record last verified: 2010-10

Locations

IT (2)