Stem Cell Transplantation in Patients With Primary Biliary Cirrhosis

NCT00393185 | Withdrawn Phase 1 DMC

• 1 other identifier: PBC
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Primary Biliary Cirrhosis

Keywords

Immunosuppression; Primary Biliary Cirrhosis; Allogeneic Hematopoietic Stem Cell

Outcome Measures

Primary Outcomes (1)

• 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

  5 years after transplant

Interventions

Non-myeloablative Hematopoietic Stem Cell Transplantation BIOLOGICAL

autologous Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• Poor performance status (ECOG \> 2) at the time of entry
• Serum bilirubin \> 4.0 mg/dl
• Significant end organ damage such as:
• LVEF \< 40% or deterioration of LVEF during exercise test on MUGA or echocardiogram
• Untreated life-threatening arrhythmia
• Active ischemic heart disease or heart failure
• End-stage lung disease characterized by DLCOadj \< 45% of predicted value
• 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

Sponsors & Collaborators

• Richard Burt, MD: lead
• Northwestern Memorial Hospital: collaborator

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 24, 2006
• First Posted: October 26, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: October 8, 2012

Record last verified: 2012-10