ACT34-CMI -- Adult Autologous CD34+ Cells

Lisata Therapeutics

Status and phase: Completed; Phase 2

Conditions: Myocardial Ischemia

Treatments: Biological: CLBS14 (low-dose); Biological: CLBS14 (high-dose); Biological: placebo injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT00300053

24779

Details and patient eligibility

About

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

Full description

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.

Enrollment: 321 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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321 participants in 3 patient groups, including a placebo group

CLBS14: Low-Dose Group

Experimental group

Description:

10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10\^5 (=100000) cells/kg bodyweight

Treatment:

Biological: CLBS14 (low-dose)

CLBS14: High-Dose Group

Experimental group

Description:

10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10\^5 (=500000) cells/kg bodyweight

Treatment:

Biological: CLBS14 (high-dose)

Placebo injection

Placebo Comparator group

Description:

10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma

Treatment:

Biological: placebo injection