Study of Autologous Bone Marrow Derived Mononuclear Cells for Treatment of Ebstein Anomaly

This study is an open label Phase I trial to determine the safety and feasibility of bone
marrow-derived mononuclear cells to the right ventricle of subjects with Ebstein anomaly at
the time of a planned surgical Ebstein repair compared to the control group undergoing the
same planned surgical intervention without the cell delivery add-on procedure. Subjects will
be screened at outpatient clinic visits at Mayo Clinic and interested qualified subjects will
be consented and offered participation in this trial. Subject/Family will decide to
participate in cell delivery or control arm. Once informed consent has been obtained,
subjects will undergo identical evaluation (other than Hematology consultation and BM harvest
occurring only in the cell-treatment group),preoperative values will be established/confirmed
and a selection committee will review subjects within three days prior to planned procedure
to confirm inclusion and exclusion criteria.However, individuals at high-risk, primarily
neonates and those with preoperative advanced right heart failure will NOT be included such
that the risk of this add-on procedure may not be acceptable. Following surgical Ebstein
repair for the control group and following cell-based product delivery for the treatment
group, all subjects will be followed for 24-months according to a pre-determined schedule
that includes imaging studies along with a questionnaire, electrophysiology and laboratory
studies at 1, 6, and 24 months post procedure. All subjects will be contacted for
surveillance by phone at 3, 12, and 18 month post procedure.

Inclusion Criteria:

- Age 6 months to 30 years

- Individuals clinically planned for elective surgical Ebstein repair

- Individuals able to undergo bone marrow aspirate according to clinical consultation
with Hematology (cell treatment group only)

- Individuals able to undergo preoperative MRI or CT examination

- Individual and/or parent willing and able to give informed consent and willing to
commit to completion of follow-up

Exclusion Criteria:

- Individuals requiring cavopulmonary shunt at the time of surgical Ebstein repair;
planned preoperatively or required intraoperatively

- Individuals with, or reasonably expected to have, complications during surgical
Ebstein repair or during post-operative recovery

- Individual who have not completed or will not be completing all pre-procedure work-up
within 30 days of surgical Ebstein repair AND lack of pre-procedure work-up documented
as a safety concern by a site investigator

- Individuals who have other clinical concerns as documented by a site investigator that
could reasonably increase the risk of complications during or after surgical Ebstein
repair

- Individuals whose cells have been determined, by the sponsor, to not be acceptable for
release to the investigational site or individual whose cells have been compromised
after cells released to investigational site (cell treatment group only)

- Individuals who require surgery on pulmonary, mitral, or aortic valve

- Individuals with pulmonary atresia or atrioventricular discordance with
ventriculoarterial discordance

- Individuals with history of ventricular arrhythmia or new onset ventricular arrhythmia
after enrollment that requires medical management

- Individuals who have undergone previous sternotomy

- Individuals with preoperative ventricular arrhythmia requiring medical management

- Individuals with severe chronic diseases, extensive extra-cardiac syndromes, or
history of any cancer

- Individuals with current IV inotrope requirements

- Individuals with bleeding disorders or history of thrombosis

- Subjects not eligible for MRI or CT examination due to either a medical
contraindication, including acute or chronic renal failure

- Individuals with a currently active infection being treated with oral antibiotics

- Individuals with the following conditions within 60 days prior to Ebstein repair
surgery:

- Cardiogenic shock or extracorporeal circulation

- Documented infection requiring treatment with intravenous antibiotics

- Cardiac condition requiring emergency procedure

- Current or uncontrolled seizures or neurological injury that has resulted in a
persistent deficit

- Multi-system organ failure including acute or chronic renal failure

- Female subjects 10 years and older with positive pregnancy test or lack of effective
birth control method during the 30 days prior to surgical Ebstein repair

- Individuals who weigh more than 90 kg