ACT34-CMI -- Adult Autologous CD34+ Cells
Condition: Myocardial Ischemia
MeSH terms: Myocardial Ischemia; Coronary Artery Disease; Ischemia
Intervention: CLBS14 (low-dose); CLBS14 (high-dose); placebo injection
Intervention description: Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 1 x 10^5 (=100000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.; Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 5 x 10^5 (=500000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.; Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Placebo will be delivered in 10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma into the target areas of myocardial ischemia.
Intervention MeSH terms: Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 321.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: angina

Summary:

      The purpose of this study is to evaluate the efficacy and safety of intramyocardial
      injections of CLBS14 in patients with refractory chronic myocardial ischemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory
             angina

          -  subjects without control of their angina symptoms, in spite of maximal tolerated doses
             of anti-anginal drugs, must be on optimal therapy for their angina and on a stable
             anti-anginal medication regimen for at least 1 month prior to entering the screening
             period of the study

          -  identified as unsuitable for conventional revascularization

          -  recent coronary angiogram (within the last 12 months) to document the coronary anatomy
             and to verify the revascularization procedures

          -  subjects must have objective evidence of inducible ischemia or viable myocardium in
             the potential target injection zone

          -  a left ventricular ejection fraction equal to or greater than 25% by ECHO or single
             photon emission computed tomography (SPECT) at screening

          -  subjects must experience at minimum an average of 7 angina or anginal equivalent
             episodes per week

          -  subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes
             on a treadmill following the Modified Bruce Protocol

          -  subjects must experience angina or anginal equivalent episodes during the screening
             exercise treadmill test

          -  female subjects must either be no longer capable of reproduction or using medically
             valid contraception to prevent pregnancy during the study

          -  subjects must be willing and able to comply with specified follow-up evaluations

        Exclusion Criteria:

          -  predominant congestive heart failure

          -  myocardial infarction within 60 days of treatment

          -  successful or partially successful coronary revascularization procedures (any vessel)
             within 6 months of study enrollment

          -  placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT)
             for heart failure in the past 90 days

          -  documented stroke or transient ischemic attack (TIA) within 60 days of study
             enrollment

          -  history of moderate to severe aortic stenosis or severe aortic insufficiency; severe
             mitral stenosis or severe mitral insufficiency

          -  prosthetic aortic valve replacement

          -  evidence of any life-threatening arrhythmia that requires intervention on the 24-hour
             Holter monitor. Life-threatening arrhythmia that is successfully treated with an
             implantable cardioverter defibrillator (ICD) is not exclusionary.

          -  splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy
             of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive
             pulmonary disease, renal failure or cancer [exceptions: in-situ skin cancer or fully
             removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5
             years with no history of a stem cell transplant])

          -  sickle cell disease or sickle cell trait

          -  platelet count greater than 10% above the upper limit of normal or a platelet count
             below 100,000 if on Clopidogrel or 50,000 without Clopidogrel

          -  hematocrit <30%

          -  serum creatinine >2.5 mg/dL

          -  any clinically significant laboratory abnormality on screening laboratories

          -  currently enrolled in another IDE or IND that has not completed the protocol required
             primary follow-up period (excludes 15 year follow up of gene therapy trials)

          -  history of alcohol or drug abuse within 3 months of screening

          -  joint or peripheral vascular disease or neurologic disease that severely limits
             treadmill walking

          -  chronic obstructive pulmonary disease that severely limits walking or FEV1 <30%
             predicted

          -  females who are pregnant or lactating

          -  female subjects who are capable of reproduction and will not use medically valid
             contraception to prevent pregnancy during the study

          -  subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic
             immunosuppressive medications or have had a prior stem cell transplant

          -  subjects with a known hypersensitivity to E. coli-derived proteins, or to any
             component of Neupogen (Filgrastim) or G-CSF

          -  subjects who have a significant psychiatric disorder or mental disability that could
             interfere with the subject´s ability to provide informed consent and/or comply with
             protocol procedures