ACT34-CMI -- Adult Autologous CD34+ Cells

Phase 2

Completed

• Conditions: Myocardial Ischemia
• Interventions: Biological: CLBS14 (low-dose); Biological: CLBS14 (high-dose); Biological: placebo injection

• Registration Number: NCT00300053
• Lead Sponsor: Lisata Therapeutics, Inc.

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2006-03-06
• Study First Submitted QC: 2006-03-06
• Study First Posted: 2006-03-08
• Study Start: 2006-04
• Primary Completion: 2008-03
• Study Completion: 2009-03
• Disposition First Submitted: 2009-10-28
• Disposition First Submitted QC: 2009-10-28
• Disposition First Posted: 2009-10-30
• Results First Submitted: 2015-12-18
• Results First Submitted QC: 2020-12-15
• Status Verified: 2021-01
• Results First Posted: 2021-01-08
• Last Update Submitted: 2021-01-08
• Last Update Posted: 2021-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 321

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CLBS14: Low-Dose Group	CLBS14 (low-dose)	10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10\^5 (=100000) cells/kg bodyweight
CLBS14: High-Dose Group	CLBS14 (high-dose)	10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10\^5 (=500000) cells/kg bodyweight
Placebo injection	placebo injection	10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma

Primary Outcome Measures

Name	Time	Method
Number of Angina Episodes Per Week at 6 and 12 Months	6 and 12 months	The number of angina episodes were collected via an electronic subject diary for four weeks at Baseline and at 6 and 12 months. The four-week angina episodes (per week mean) were used as the frequency for each visit. A lower number represents fewer angina episodes. A lower number is better.

Secondary Outcome Measures

Name	Time	Method
Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise	Change from Baseline to 6 months and change from baseline to 12 months after treatment	A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.
Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months	Baseline to 6 months after treatment	Angina symptoms were evaluated based on the Seattle Angina Questionnaire (SAQ), which was used to analyze the following: physical limitations, angina stability, angina frequency, treatment satisfaction, and disease perception. The SAQ consisted of 11 questions with 5 or 6 possible responses. Responses were ordinal values (1-7, 10, 11, 97, depending on the type of question; no uniform ranges throughout); responses that corresponded to the lowest level of functioning (worse outcomes) were assigned values of 1, while responses that corresponded to higher functioning levels (better outcome) were assigned a higher ordinal value. If the response to any of these questions was 97 it was recoded as a missing value. Each scale can have a scored value ranging from 0 to 100. A larger number is better.
Change in Anti-anginal Medication (ie, Nitroglycerin) Use	Baseline to 6 months	The mean nitroglycerin use per week was analyzed at baseline and 6 months
Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels	Baseline and 12 months after treatment	The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows: * Class I - Angina only during strenuous or prolonged physical activity; * Class II - Slight limitation, with angina only during vigorous physical activity; * Class III - Symptoms with everyday living activities, i.e., moderate limitation; * Class IV - Inability to perform any activity without angina or angina at rest, i.e., severe limitation
Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters	Baseline to 6 months after treatment	The Short Form 36 (SF-36) health survey form was used to analyze physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health, and health transition. Responses were coded as ordinal numbers going from worst (=1) to best (=highest number). These ordinal scores were transformed into scales ranging from 0 to 100. Higher numbers are generally considered better.

Trial Locations

Locations (25)

Northwestern University Medical Center, Bluhm Cardiovascluar Institute; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Scripps Memorial Hospital; 🇺🇸 La Jolla, California, United States

Stanford University Hospital and Clinics; 🇺🇸 Stanford, California, United States

Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Central Florida Cardiology Group; 🇺🇸 Orlando, Florida, United States

University of Florida Health Science Center; 🇺🇸 Jacksonville, Florida, United States

Saint Joseph's Research Institute; 🇺🇸 Atlanta, Georgia, United States

University of Iowa Hospitals & Clinic; 🇺🇸 Iowa City, Iowa, United States

Caritas Saint Elizabeth's Medical Center; 🇺🇸 Boston, Massachusetts, United States

New York Presbyterian Hospital - Columbia University Medical Center; 🇺🇸 New York, New York, United States

New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University; 🇺🇸 New York, New York, United States

University Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Swedish Heart & Vascular - Swedish Medical Center; 🇺🇸 Seattle, Washington, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Comprehensive Cardiovascular Care Group; 🇺🇸 Milwaukee, Wisconsin, United States

University of Wisconsin Medical School; 🇺🇸 Madison, Wisconsin, United States

Arizona Heart Institute; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Abbott Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

The Lindner Clinical Trial Center; 🇺🇸 Cincinnati, Ohio, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cardiology PC; 🇺🇸 Birmingham, Alabama, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States