Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)

Heart failure remains a major public health problem, affecting 5 million patients in the US
with 550,000 new diagnoses made each year. Heart failure is the leading cause of
hospitalization in persons over 65 years of age with cost exceeding $29 billion annually.
Prognosis is very poor once a patient has been hospitalized with heart failure. The mortality
risk after heart failure hospitalization is 11.3% at 30 days, 33.1% at 1 year and well over
50% within 5 years (Hunt SA; et al., 2005). These numbers emphasize the need to develop and
implement more effective treatments to manage heart failure.

This study is targeting a subset of heart failure patient population, namely those diagnosed
with dilated cardiomyopathy (DCM). The World Health Organization (WHO) defines dilated
cardiomyopathy as a cardiac condition wherein a ventricular chamber exhibits increased
diastolic and systolic volume and a low (<40%) ejection fraction. DCM is reported to affect
108,000 to 150,000 patients in the U.S.

This study is a prospective, stratified, randomized, open-label, controlled, multi-center
study to assess the safety profile and efficacy of CRCs in treating patients with DCM. It
will enroll a total of 40 patients at 5 sites in the U.S.

Inclusion Criteria:

- Diagnosis of ischemic or nonischemic DCM according to World Health Organization
criteria; OR ischemic DCM (DCM in a patient with a history of myocardial infarction or
evidence of clinically significant (>/= 70% narrowing of a major epicardial artery)
coronary artery disease)

- No other cardiac surgery or percutaneous cardiac interventions likely to produce
clinical improvement, in the opinion of the investigator and the referring
interventional cardiologist

- Left ventricular ejection fraction
- Symptomatic heart failure in NYHA functional class III or IV

- Able to comply with scheduled visits in cardiac out-patient clinic

- Able to tolerate study procedures, including bone marrow aspiration, left lateral
thoracotomy or thoracoscopy with single lung ventilation, MRI or cardiac CT,
spirometry and 6 minute walk test

- Males and females, 18-86 years of age

- Life expectancy of 6 months or more in the opinion of investigator

- Able to give informed consent

- Normal organ and marrow function (Leukocytes >/= 3,000/microgram, Absolute neutrophil
count >/= 1,500/microgram, Platelets >/= 140,000/microgram, AST (SGOT)/ALT (SGPT) 2.5 x institutional standards range) and Creatinine
- Adequate pulmonary function (forced expiratory volume in one second [FEV1] > 50%
predicted)

- Controlled blood pressure (systolic blood pressure into the study

- Adequate medical management of DCM and other pre-existing conditions. Drug treatment
regimen must have been established for at least a month prior to randomization in
eligible patients.

- Fertile patients must agree to use an appropriate form of contraception while
participating in the study

Exclusion Criteria:

- Severe primary valvular insufficiency(ies)

- Known history of Chronic Obtrusive Pulmonary Disease (Gold stages IIB or more severe
only) or restrictive pulmonary disease

- Known history of primary pulmonary hypertension

- Ventricular Assist Device implantation

- Myocardial infarction within 4 weeks of randomization

- Life-threatening ventricular arrhythmia, except if implantable cardioverter
defibrillator is implanted

- Unstable angina, characterized by increasingly frequent episodes with modest exertion
or at rest, worsening severity, and prolonged duration

- Patients receiving treatment with hematopoietic growth factors

- Patients who require uninterruptible anticoagulation or anti-platelet therapy [i.e.
anticoagulation therapy (e.g. warfarin) that cannot be stopped for 72 hours prior to
bone marrow aspiration and intramyocardial injections]

- Patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for
7 days prior to bone marrow aspiration and intramyocardial injections

- Known cancer and undergoing treatment including chemotherapy and radiotherapy

- Patients who will require continuous, systemic, high dose corticosteroid therapy (more
than 7.5 mg/day) within 6 months after surgery

- End stage renal disease requiring dialysis

- Patients pregnant or lactating; positive for hCG

- History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1
drink = 5 oz of wine or 12 oz [360mL] of beer or 1.5 oz [45mL] of hard liquor) or
history of illicit drug use within 6 months of screening

- Known allergies to protein products (horse or bovine serum, or porcine trypsin)

- Body Mass Index of 40 Kg/m2 or greater

- Patients receiving experimental medications or participating in another clinical study
within 30 days of screening

- HIV or syphilis, positive at time of screening

- Active Hepatitis B, or Hepatitis C infection at time of screening

- In the opinion of the investigator, patient is unsuitable for cellular therapy

- Patients receiving anti-angiogenic drugs