ACT34-CMI -- Adult Autologous CD34+ Cells

NCT ID: NCT00300053

Last Updated: 2021-01-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

321 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2009-03-31

Brief Summary

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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

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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.

Conditions

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Myocardial Ischemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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CLBS14: Low-Dose Group

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

Group Type EXPERIMENTAL

CLBS14 (low-dose)

Intervention Type BIOLOGICAL

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.

CLBS14: High-Dose Group

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

Group Type EXPERIMENTAL

CLBS14 (high-dose)

Intervention Type BIOLOGICAL

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.

Placebo injection

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

Group Type PLACEBO_COMPARATOR

placebo injection

Intervention Type BIOLOGICAL

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.

Interventions

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CLBS14 (low-dose)

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.

Intervention Type BIOLOGICAL

CLBS14 (high-dose)

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.

Intervention Type BIOLOGICAL

placebo injection

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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G-CSF mobilized, autologous CD34+ cells G-CSF mobilized, autologous CD34+ cells 0.9% NaCl (saline) in 5% autologous plasma

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lisata Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Caladrius Study DIrector

Role: STUDY_DIRECTOR

Lisata Therapeutics, Inc.

Locations

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Cardiology PC

Birmingham, Alabama, United States

Site Status

Arizona Heart Institute

Phoenix, Arizona, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Scripps Memorial Hospital

La Jolla, California, United States

Site Status

Stanford University Hospital and Clinics

Stanford, California, United States

Site Status

Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

University of Florida Health Science Center

Gainesville, Florida, United States

Site Status

University of Florida Health Science Center

Jacksonville, Florida, United States

Site Status

Central Florida Cardiology Group

Orlando, Florida, United States

Site Status

Saint Joseph's Research Institute

Atlanta, Georgia, United States

Site Status

Northwestern University Medical Center, Bluhm Cardiovascluar Institute

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals & Clinic

Iowa City, Iowa, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Caritas Saint Elizabeth's Medical Center

Boston, Massachusetts, United States

Site Status

Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University

New York, New York, United States

Site Status

The Lindner Clinical Trial Center

Cincinnati, Ohio, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Swedish Heart & Vascular - Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin Medical School

Madison, Wisconsin, United States

Site Status

Comprehensive Cardiovascular Care Group

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 21737787 (View on PubMed)

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.

Reference Type RESULT
PMID: 27151378 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23137499 (View on PubMed)

Other Identifiers

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24779

Identifier Type: -

Identifier Source: org_study_id

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