Clinical trial NCT00300053: ACT34-CMI -- Adult Autologous CD34+ Cells
Official title: A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Ischemia
Keywords: angina
Lead sponsor: Lisata Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-03-08
Enrollment: 321
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Angina Episodes Per Week at 6 and 12 Months
timeFrame: 6 and 12 months
Secondary outcomes:
measure: Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
timeFrame: Change from Baseline to 6 months and change from baseline to 12 months after treatment
measure: Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
timeFrame: Baseline and 12 months after treatment
measure: Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
timeFrame: Baseline to 6 months after treatment
measure: Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
timeFrame: Baseline to 6 months after treatment
measure: Change in Anti-anginal Medication (ie, Nitroglycerin) Use
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Heart Institute
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: La Jolla
country: United States
facility: Scripps Memorial Hospital
state: California
city: Stanford
country: United States
facility: Stanford University Hospital and Clinics
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Orlando
country: United States
facility: Central Florida Cardiology Group
state: Florida
city: Atlanta
country: United States
facility: Saint Joseph's Research Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical Center, Bluhm Cardiovascluar Institute
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinic
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Caritas Saint Elizabeth's Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: New York
country: United States
facility: New York Presbyterian Hospital - Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
state: New York
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Swedish Heart & Vascular - Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Medical School
state: Wisconsin
city: Milwaukee
country: United States
facility: Comprehensive Cardiovascular Care Group
state: Wisconsin
Study officials:
affiliation: Lisata Therapeutics, Inc.
name: Caladrius Study DIrector
role: STUDY_DIRECTOR
References:
citation: Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA; ACT34-CMI Investigators. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011 Aug 5;109(4):428-36. doi: 10.1161/CIRCRESAHA.111.245993. Epub 2011 Jul 7.
citation: Henry TD, Schaer GL, Traverse JH, Povsic TJ, Davidson C, Lee JS, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Patel AN, Riedel N, Junge C, Hunt A, Kereiakes DJ, White C, Harrington RA, Schatz RA, Losordo DW; ACT. Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study. Cell Transplant. 2016;25(9):1701-1711. doi: 10.3727/096368916X691484. Epub 2016 May 4.
citation: Povsic TJ, Losordo DW, Story K, Junge CE, Schatz RA, Harrington RA, Henry TD. Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI. Am Heart J. 2012 Nov;164(5):689-697.e3. doi: 10.1016/j.ahj.2012.06.022.