A Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency
Condition: Liver Disease
MeSH terms: Liver Diseases; Hepatic Insufficiency; Liver Failure
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a prospective dose escalation study of the administration of adult human stem cells
      in patients with end stage liver failure. Successive groups of two patients will receive
      ascending doses of autologous adult human stem cells starting at 1x10[9] cells. Following
      expansion in an approved Good Manufacturing Practice (GMP) facility the cells will be infused
      into either the hepatic artery or portal vein of research participants.

      The aim of this trial is to determine the maximum tolerated dose of autologous adult stem
      cells when infused into either the hepatic artery or the portal vein. The maximum dose that
      would be given would be 5x10 to the ten [10].

      To assess improvement in liver function as measured by serological and biochemical analysis
      and determine whether there are any symptomatic improvements as reported by the patients.
    

Detailed description: 
      This is a prospective dose escalation study of the administration of expanded autologous
      adult human stem cells in patients with chronic liver insufficiency. Four groups of two
      patients will receive ascending doses of autologous adult human stem cells starting at a dose
      of 1 x 10[8] cells. The cells will be infused into either the hepatic artery or the portal
      vein of research participants. The consultant radiologist will review a duplex Doppler scan
      of the blood supply to the liver to determine the safest route for delivery of the cells.

      The first patients (01 and 02) will receive 1 x 10[8] cells. If no adverse events are
      observed in either patient in the two-week period post stem cell administration, patient
      numbers 03 and 04 will receive 5 x 1[08] cells. This will continue through patients 05 and 06
      receiving cells at 1 x 10[9] and 07 and 08 receiving 5 x 10[9] cells. If any patient in any
      cohort suffers adverse events considered to be treatment-related, the next group of patients
      will receive cells at a concentration one step down from that received by the patient
      suffering the adverse events.

      At the completion of this first stage of the study, if no adverse treatment related events
      are seen, a further group of 10 patients will receive cells at a concentration of 5 x 10[9]
      cells.

      It should be noted that if fewer cells are obtained at the end of the expansion period the
      re-infusion of the cells to the patient should nonetheless continue. This patient will be
      considered inevaluable and the next participant will be allocated their trial number.

      The total period that each patient will be participating in the study is 12 weeks and the
      total duration of this clinical trial is expected to be approximately 12 months.

      All patients will be assessed 4 weeks after coming off study (week 12), whether from
      completion of protocol or early withdrawal for whatever reason. They will also be monitored
      in the clinic for the remainder of their life.

      Patients who are withdrawn due to issues of toxicity will be followed until the adverse event
      is resolved or the outcome is known. Patients will then be followed-up for four weeks after
      resolution and thereafter for life in the clinic.
    

Intervention name(s): Autologous Expanded CD34+ Haemopoietic cells
Intervention type(s): Biological
Intervention description(s): Autologous expanded CD34+ cells obtained by leukapheresis on a single occasion by infusion into the hepatic artery or portal vein.
Patient numbers 01 and 02 will receive 1x109 cells Patient numbers 03 and 04 will receive 1x1010 cells Patient numbers 05 and 06 will receive 2x1010 cells Patient numbers 07 and 08 will receive 5x1010 cells
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Adult stem cell therapy