act34-cmi -- adult autologous cd34+ cells

Conditions: Myocardial Ischemia

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.

this is a double-blind, prospective, randomized, placebo-controlled trial to determine the tolerability, efficacy, safety and dose range of intramyocardial injections of adult autologous cd34+ cells mobilized with granulocyte colony stimulating factor (g-csf) for the reduction of angina episodes 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

Keywords: angina