ACT34-CMI -- Adult Autologous CD34+ Cells
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)
1 other identifier
interventional
321
1 country
26
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2006
Typical duration for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 6, 2006
CompletedFirst Posted
Study publicly available on registry
March 8, 2006
CompletedStudy Start
First participant enrolled
April 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2009
CompletedResults Posted
Study results publicly available
January 8, 2021
CompletedJanuary 26, 2021
January 1, 2021
1.9 years
March 6, 2006
December 18, 2015
January 8, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Angina Episodes Per Week at 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.
6 and 12 months
Secondary Outcomes (5)
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
Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
Baseline and 12 months after treatment
Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
Baseline to 6 months after treatment
Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
Baseline to 6 months after treatment
Change in Anti-anginal Medication (ie, Nitroglycerin) Use
Baseline to 6 months
Study Arms (3)
CLBS14: Low-Dose Group
EXPERIMENTAL10 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
EXPERIMENTAL10 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 COMPARATOR10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- 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
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Cardiology PC
Birmingham, Alabama, 35211, United States
Arizona Heart Institute
Phoenix, Arizona, 85005, United States
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
Scripps Memorial Hospital
La Jolla, California, 92037, United States
Stanford University Hospital and Clinics
Stanford, California, 94305, United States
Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Holy Cross Hospital
Fort Lauderdale, Florida, 33308, United States
University of Florida Health Science Center
Gainesville, Florida, 32610, United States
University of Florida Health Science Center
Jacksonville, Florida, 32209, United States
Central Florida Cardiology Group
Orlando, Florida, 32803, United States
Saint Joseph's Research Institute
Atlanta, Georgia, 30342, United States
Northwestern University Medical Center, Bluhm Cardiovascluar Institute
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Iowa Hospitals & Clinic
Iowa City, Iowa, 52242, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Caritas Saint Elizabeth's Medical Center
Boston, Massachusetts, 02135, United States
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
New York Presbyterian Hospital - Columbia University Medical Center
New York, New York, 10032, United States
New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
New York, New York, 10065, United States
The Lindner Clinical Trial Center
Cincinnati, Ohio, 45219, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213, United States
Swedish Heart & Vascular - Swedish Medical Center
Seattle, Washington, 98122, United States
University of Wisconsin Medical School
Madison, Wisconsin, 53792, United States
Comprehensive Cardiovascular Care Group
Milwaukee, Wisconsin, 53223, United States
Related Publications (3)
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.
PMID: 21737787RESULTHenry 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.
PMID: 27151378RESULTPovsic 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.
PMID: 23137499DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- William Sietsema
- Organization
- Caladrius Biosciences
Study Officials
- STUDY DIRECTOR
Caladrius Study DIrector
Lisata Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2006
First Posted
March 8, 2006
Study Start
April 1, 2006
Primary Completion
March 1, 2008
Study Completion
March 1, 2009
Last Updated
January 26, 2021
Results First Posted
January 8, 2021
Record last verified: 2021-01