u-STOP LVAD Bleed: Utilization of Umbilical Cord Lining Stem Cells (ULSCs) To Prevent Left Ventricular Assist Device (LVAD) Associated Angiodysplastic Bleeding
Condition: Angiodysplastic Bleeding
MeSH terms: Hemorrhage
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This is a Phase I, single ascending dose, first in human, open-label, non-controlled,
      dose-escalation trial that will investigate intravenous infusions of Umbilical cord lining
      stem cells (UCLSCs) in Left Ventricular Assist Device (LVAD) patients.

      This study will recruit patients from the Advanced Heart Failure and LVAD Clinic at the
      University of Florida, including recently implanted patients, as well as patients on chronic
      long-term support, with the goal of enrolling up to 9 subjects to participate in the study.
    

Detailed description: 
      Subjects will be entered into a 3+3 dose escalation study, a standard design for initial
      trials to evaluate tolerability of a therapeutic agent and identify a maximal tolerated dose
      if indeed toxicities are identified in the pre-specified dosing range. The first 3 subjects
      will be administered 50 x 10^6 ULSCs reconstituted in PBS with 1% human serum albumin in a
      volume of 250 ml, and monitored for adverse events or toxicities, immediately following
      dosing, and again at 30 days. Safety endpoints will be reviewed by the DSMB and depending on
      the response, the dose will be escalated to 100 x 10^6 and 200 x 10^6 ULSC in a constant 250
      ml volume. We will enroll only 9 subjects in the case that no subject experiences toxicity,
      only expanding the cohort in the event that a subject experiences toxicity at a particular
      dose.

      This specific dose escalation approach is based on the following considerations:

      There is not yet a standard dosing regimen for cell therapy in heart failure patients. The
      previous MSC trial in LVAD patients provided 150 million cells. The RIMECARD trial
      (Bartolucci et al, Circ Res 2017 Oct 27;121(10):1192-1204. PMID 28974553) provided umbilical
      cord-derived MSC for patients with heart failure via intravenous infusions of 1x106 cells/kg.
      Similarly, another Phase IIa trial of MSCs in HFrEF used 1.5x106 cells/kg (Butler et al.,
      Circ Res 2017 Jan 20;120(2):332-340. PMID 27856497). Since our LVAD patients range in size
      from 50 to > 100kg, we believe the selected range of doses is reasonable for this patient
      population.

      In addition, in ongoing studies in COVID 19 ARDS, IND# 19979, we have provided 100 x 106
      ULSCs with no adverse safety signals. Moreover, in our non-clinical animal models, we
      demonstrated safety at doses ranging from a high dose of 1 x 106 cells/mouse, which is
      equivalent to approximately 5 x 107 cells/kg in humans and a low dose of 5 x 104 cells/mouse
      which is equivalent to approximately 2.5 x 106 cells/kg in humans. The dose tested in the
      high dose preclinical study would scale to administration of over 2.5 billion cells in an
      individual weighing 100 pounds.
    

Intervention name(s): Intravenous Infusion of UCLSCs
Intervention type(s): Drug
Intervention description(s): The first 3 subjects will be administered 50 x 10^6 ULSCs reconstituted in PBS with 1% human serum albumin in a volume of 250 ml, and monitored for adverse events or toxicities, immediately following dosing, and again at 30 days.
Intervention model: Single Group Assignment
Intervention model description: Subjects will be entered into a 3+3 dose escalation study, a standard design for initial trials to evaluate tolerability of a therapeutic agent and identify a maximal tolerated dose if indeed toxicities are identified in the pre-specified dosing range.
Masking: None (Open Label)
Primary purpose: Other