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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01020968
• Date of registration: 25/11/2009
• Primary sponsor: Aastrom Biosciences
• Public title: Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
• Scientific title: Catheter-based Transendocardial Delivery of Autologous Bone Marrow-Derived Cells in Patients With Heart Failure Due to Dilated Cardiomyopathy
• Date of first enrolment: December 2009
• Target sample size: 24
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT01020968
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Timothy Henry, MD
• Affiliation: Minneapolis Heart Institute Foundation

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of ischemic or non-ischemic dilated cardiomyopathy according to WHO
criteria. Ischemic: 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. Non-ischemic: Dilation and impaired contraction of left
ventricle or both ventricles of idiopathic, familial/genetic, viral and/or immune,
toxic origin, or associated with recognized cardiovascular disease in which the
degree of myocardial dysfunction is not explained by normal loading conditions or the
extent of ischemic damage.

- No other cardiac surgery or percutaneous cardiac interventions likely to produce
clinical improvement, as determined by an interventional cardiologist (for PTCA) and
a cardiothoracic surgeon (for CABG). This condition is satisfied in patients
w/chronic ischemic disease who have previously been successfully revascularized but
have failed to show clinical improvement. All patients who are candidates for
revascularization are ineligible for participation.

- LVEF
- Symptomatic heart failure in NYHA class III or IV.

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

- Able to tolerate study procedures, including bone marrow aspiration, cardiac CT,
metabolic stress test,6 minute walk test.

- Males and females, 18-86 years of age.

- Life expectancy of 6 months or more in the opinion of the 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
- Controlled blood pressure (systolic blood pressure into the study.

- Stable, standard medical therapy for DCM for at least 1 month with NO new medications
to treat the disease introduced in the last 3 months. Standard medical therapy
includes: Placement of AICD unless contraindicated (refusal of AICD not considered
valid contraindication), use of ACE inhibitors and/or AT-1 receptor blockers as well
as loop diuretics unless contraindicated and, depending on the type of heart failure
associated with the disease, standard therapy may also include use of vasodilators,
beta blockers, digoxin, and aldosterone or other medications.

- Pre-existing conditions are adequately controlled in the opinion of the investigator.

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

Exclusion Criteria:

- Severe primary valvular heart disease including, but not limited to, aortic valve
stenosis and insufficiency.

- Known history of COPD defined as Gold stage IIB (FEV1/FVC<70% with 30% predicted, with or without chronic symptoms of cough, sputum production, dyspnea) or
more severe or restrictive pulmonary disease.

- Known history of primary pulmonary hypertension.

- VAD implantation.

- Myocardial infarction within 4 weeks prior to randomization.

- History of life-threatening ventricular arrhythmia, except if an AICD is implanted.

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

- Patients at high risk for complications due to injection procedure (e.g. patients who
have severe peripheral atherosclerotic disease that does not allow advancement of the
catheter; patients who have a prosthetic aortic or mitral valve; patients who have a
LV thrombus or aneurysm; patients who have an aortic dissection or aneurysm, etc.).

- Patients w/poorly controlled diabetes mellitus (HbAlc>9.0%).

- Patients receiving treatment with hematopoietic growth factors (e.g. EPO, G-CSF).

- Patients who require uninterruptible anticoagulation therapy (e.g. warfarin)that
cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial
injections; OR patients receiving anti-platelet therapy (e.g. clopidogrel) that
cannot be stopped for 7 days prior to bone marrow aspiration and transendocardial
injections, unless contraindicated.

- Known cancer and undergoing treatment including chemotherapy and radiation.

- Patients requiring continuous, systemic, high dose corticosteroid therapy (more than
7.5 mg/day) within 1 month before aspiration or 6 months after injection procedure.

- 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 w/in 6 months of screening.

- Known allergies to protein products (horse or bovine serum, or porcine trypsin) used
in the ex-vivo cell production process.

- BMI 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 the time of screening.

- Patient determined unsuitable for cellular therapy, in the opinion of the
investigator or sponsor.

- Patients receiving anti-angiogenic drugs (e.g. anti-VEGF).

- Known allergy or sensitivity to contrast agents used in imaging procedures.

- Minimum LV wall thickness of less than 6mm as determined by ECHO.



Age minimum: 18 Years
Age maximum: 86 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Dilated Cardiomyopathy

Intervention(s)

Biological: Cardiac Repair Cells (CRCs)

Primary Outcome(s)

Incidence of major adverse cardiac event (MACE) (MACE defined as: cardiac death, cardiac arrest, myocardial infarction, sustained ventricular arrhythmias, pulmonary edema, acute heart failure, unstable angina and major bleeding) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Secondary Outcome(s)

AICD firing rate [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Angina status (As determined by Canadian Cardiovascular Society (CCS) classification and Troponin I Levels) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Assessment of myocardial perfusion in ischemic patient cohort, only (As determined by SPECT) [Time Frame: Baseline and Month 3]

Change in LV and RV dimensions and in LV volumes (As determined by Echo, Cardiac CT and SPECT) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12. CT and SPECT are only assessed at Baseline and Month 6.]

Changes in medication for heart failure [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Device implantation, transplantation and positive inotrope use (As determined by incidence rates) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Exercise tolerance (6 minute walk test) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Heart failure status (As determined by New York Heart Association (NYHA) heart failure status (NYHA) class and Brain Natriuretic Peptide [BNP]) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Left ventricular ejection fraction (LVEF) (As determined by Echo, Cardiac CT and SPECT) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12. CT and SPECT are only assessed at Baseline and Month 6.]

Pulmonary function (As determined by metabolic stress test) [Time Frame: Baseline, Month 6 and Month 12]

Quality of life (As determined by Minnesota Living with Heart Failure Questionnaire [MLHFQ]) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12]

Wall Motion Score Index (WMSI) (As determined by Echo, Cardiac CT and SPECT) [Time Frame: Outcome measures will generally be assessed at Baseline, Month 3, Month 6 and Month 12. CT and SPECT are only assessed at Baseline and Month 6.]

Secondary ID(s)

ABI-55-0811-1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors