Stem Cell Transplantation in Patients With Primary Biliary Cirrhosis

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Northwestern Memorial Hospital
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00393185
First received: October 24, 2006
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

This disease is believed to be due to immune cells, cells which normally protect the body, but are now destroying the bile ducts in the liver. When the ducts are damaged, bile builds up in the liver and damages liver tissue. Over time, the disease can cause cirrhosis and may make the liver stop working. This study is designed to examine whether treating patients with high dose Cyclophosphamide and Fludarabine (drugs which reduce the function of your immune system) and CAMPATH-1H (a protein that kills the immune cells that are thought to be causing PBC), followed by return of blood stem cells that have been previously collected from patient brother or sister will stop or reverse the disease. The purpose of the Cyclophosphamide, Fludarabine and CAMPATH-1H is to decrease immune system. The purpose of the stem cell infusion is to restore blood production, which will be severely impaired by the Cyclophosphamide, Fludarabine and CAMPATH-1H, and to produce a normal immune system that will no longer attack the body.


Condition Intervention Phase
Primary Biliary Cirrhosis
Biological: Non-myeloablative Hematopoietic Stem Cell Transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-myeloablative Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Primary Biliary Cirrhosis: A Phase I Study

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • No liver-related death or LTx over the 2-year (extended to 5 years) follow-up; Normalization of serum alkaline phosphatase over 6 months;Amelioration of PBC histological stage with reduction of both inflammation and fibrosis scores 42 [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: January 2006
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Non-myeloablative Hematopoietic Stem Cell Transplantation
    autologous Hematopoietic Stem Cell Transplantation
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Patient enrollment

Inclusion Criteria:

  • Age > 55 years old at the time of evaluation
  • An established diagnosis of PBC, i.e. presence of all three diagnostic criteria, detectable serum AMA at titer >1:40, elevated alkaline phosphatase levels for > 6 months, and compatible liver histology
  • Incomplete response to UDCA at 13-15 mg/kg/day (Incomplete response is defined as elevated serum alkaline phosphatase (>2X upper normal value) after 12 months of UDCA therapy, as defined by Angulo and colleagues).

And any of the following

  • Pruritus unresponsive to medical therapy
  • Liver disease with more than 50% probability of dying or needing a LTx in the following 36 months according to the Mayo survival model(equivalent to a Mayo score higher than 6.78 (The Mayo survival model is a validated survival instrument based on age, bilirubin PT, and edema that does not require a liver biopsy).

Exclusion Criteria:

  • Poor performance status (ECOG > 2) at the time of entry
  • Serum bilirubin > 4.0 mg/dl
  • Significant end organ damage such as:

    1. LVEF < 40% or deterioration of LVEF during exercise test on MUGA or echocardiogram
    2. Untreated life-threatening arrhythmia
    3. Active ischemic heart disease or heart failure
    4. End-stage lung disease characterized by DLCOadj < 45% of predicted value
    5. Serum creatinine > 2.0 mg/dl
  • HIV positive
  • Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment
  • Prior history of malignancy except localized basal cell or squamous skin cancer; Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis
  • Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
  • Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  • Inability to give informed consent
  • Major hematological abnormalities such as platelet count < 100,000/ul or ANC < 1000/ul
  • GI bleed from portal hypertension
  • Portal HTN documented by transvenous portal vein wedge pressure greater than 20 cm H20
  • Ascites that is non-responsive to full-dose diuretics and human albumin infusion
  • Systemic sclerosis
  • AMA positive donor
  • HCV PCR positive or HBSAg positive donor
  • Failure to collect less than 2.0 x 106 CD34 cells/kg from a matched sibling
  • Patient on liver transplant list

Donor enrollment

Inclusion Criteria:

  • Donor must be a HLA identical sibling or HLA matched cord blood donor.
  • If multiple HLA matched donors are available, preference will be given to same sex, same CMV status, or in the case of cord blood higher nucleated cell count.
  • AMA negative
  • If no HLA matched sibling is available, donor may be HLA matched cord blood. The minimum number of cord blood nucleated cells available must be more than 2X107/kg. To achieve this number of nucleated cells, two units of HLA matched cord blood may be utilized (Wagner JE Blood 2005 Feb 1; 105(3): 1343-7)

Exclusion criteria:

  • Physiologic age > 50 years old or <18 years old (except cord blood units)
  • HIV positive
  • Active ischemic heart disease or heart failure
  • Acute or chronic active hepatitis
  • Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the donor to tolerate stem cell collection
  • Prior history of malignancy except localized basal cell or squamous skin cancer; Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis
  • Positive pregnancy test
  • Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  • Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00393185

Sponsors and Collaborators
Richard Burt, MD
Northwestern Memorial Hospital
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00393185     History of Changes
Other Study ID Numbers: PBC
Study First Received: October 24, 2006
Last Updated: October 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Immunosuppression
Primary Biliary Cirrhosis
Allogeneic Hematopoietic Stem Cell

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014