Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina

NCT ID: NCT01508910

Last Updated: 2018-12-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

291 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2015-11-30

Brief Summary

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The purpose of the study is to assess the safety and efficacy of targeted intramyocardial delivery of Auto-CD34+ cells for increasing exercise time and amelioration of anginal symptoms in subjects with refractory angina and chronic myocardial ischemia.

Detailed Description

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Conditions

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Chronic Myocardial Ischemia Refractory Angina Pectoris Advanced Coronary Heart Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Treatment Arm

Targeted intramyocardial delivery of 1 x 10\^5 Auto-CD34+ cells after granulocyte-colony stimulating factor (G-CSF) mobilization and apheresis

Group Type EXPERIMENTAL

Auto-CD34+ cells

Intervention Type BIOLOGICAL

10 intramyocardial injections of 0.2 mL per injection site of Auto-CD34+ cells

Active Control Arm

Targeted intramyocardial delivery of placebo after G-CSF mobilization and apheresis

Group Type PLACEBO_COMPARATOR

Placebo: Diluent used to suspend Auto-CD34+ cells

Intervention Type BIOLOGICAL

10 intramyocardial injections of 0.2 mL per injection site of placebo

Unblinded Standard of Care (SOC) Arm

No study-related procedures will be performed.

Group Type OTHER

Standard of care

Intervention Type OTHER

Standard of care for refractory angina

Interventions

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Auto-CD34+ cells

10 intramyocardial injections of 0.2 mL per injection site of Auto-CD34+ cells

Intervention Type BIOLOGICAL

Placebo: Diluent used to suspend Auto-CD34+ cells

10 intramyocardial injections of 0.2 mL per injection site of placebo

Intervention Type BIOLOGICAL

Standard of care

Standard of care for refractory angina

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Male or female participants who are 21 to 80 years of age at the time of signing the informed consent.
* Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic refractory angina.
* Participants without control of their angina symptoms in spite of maximal tolerated doses of anti-angina drugs. Participants must be on optimal therapy for their angina and must have been on a stable anti-anginal medication regimen for at least 4 weeks before signing the informed consent form.
* Participants with obstructive coronary disease unsuitable for conventional revascularization due to unsuitable anatomy or comorbidity as determined at the site and confirmed by an independent adjudication committee.
* Participants must have evidence of inducible myocardial ischemia.
* Participants must experience angina episodes.
* Participants must be able to complete 2 exercise tolerance tests on the treadmill within 3 weeks of randomization.
* If female of childbearing potential, subject must not be pregnant and agree to employ adequate birth control measures for the duration of the study.

Exclusion Criteria

* Cardiovascular hospitalization within 60 days prior to potential study enrollment. Participant has had a successful or partially successful coronary artery bypass graft (CABG) within 6 months or PCTA within 60 days of potential study enrollment.
* Participant has had a placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure within 180 days of potential study enrollment.
* Participant has documented stroke or transient ischemic attacks (TIAs) within 60 days of potential study enrollment.
* Participant has a history of moderate to severe aortic stenosis; or severe aortic insufficiency; or severe mitral stenosis; or severe mitral insufficiency.
* Participant has a prosthetic aortic valve or a mechanical mitral valve replacement.
* Participant has severe co-morbidity associated with a reduction in life expectancy to less than 3 years as a result of chronic medical illnesses.
* Participants with cancer are excluded with the following exceptions:

* Subjects with in-situ non-melanoma skin cancer or in-situ cervical cancer are not excluded.
* Participants that have been cancer free for \>= 5 years as determined by their oncologist are not excluded. Subjects with a prior history of stem cell transplant for cancer are excluded no matter how long they have been cancer-free.
* Participants with a history of leukemia or other bone marrow disease.
* Participant has sickle cell disease or sickle cell trait.
* Participants with proliferative retinopathy.
* Participants with Hb A1c \> 9%.
* Participant has platelet counts \>10% above the upper limit of normal (ULN) or platelet counts \< 70,000.
* Participant has a hematocrit \< 30% prior to potential study enrollment.
* Participant has a serum creatinine \> 2.5 mg/dL prior to potential study enrollment.
* Participant tests positive for HIV, hepatitis B, or hepatitis C, or is on chronic immunosuppressive medications, or has had a previous stem cell transplant.
* Participant has a known contraindication to Neupogen (filgrastim) or G-CSF.
* Participant was previously enrolled in an active treatment group of cell therapy trials for cardiovascular disease including any phase of CD34+ stem cell trials.
* Left ventricular (LV) thickness of \< 7 mm in the target areas of injection as measured by during a 2-D echocardiogram (ECHO).
* Atrial fibrillation, atrial flutter, or other uncontrolled arrhythmias that would prohibit accurate electromechanical mapping and NOGA-guided intramyocardial injection.
* Bleeding diathesis with an INR \> 1.8 when not receiving anti-thrombotic therapy.
* Hepatic dysfunction as evidenced by elevated AST or ALT levels \> 2.5 x ULN.
* Any previous transplant requiring immunosuppression.
* Disease state requiring chronic immunosuppression.
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

Caladrius Biosciences

Locations

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Birmingham, Alabama, United States

Site Status

Gilbert, Arizona, United States

Site Status

Phoenix, Arizona, United States

Site Status

La Jolla, California, United States

Site Status

Los Angeles, California, United States

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Oxnard, California, United States

Site Status

San Diego, California, United States

Site Status

Stanford, California, United States

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Boynton Beach, Florida, United States

Site Status

Daytona Beach, Florida, United States

Site Status

Gainesville, Florida, United States

Site Status

Jacksonville, Florida, United States

Site Status

Miami, Florida, United States

Site Status

Orlando, Florida, United States

Site Status

Tampa, Florida, United States

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Atlanta, Georgia, United States

Site Status

Augusta, Georgia, United States

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Chicago, Illinois, United States

Site Status

Iowa City, Iowa, United States

Site Status

Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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Saginaw, Michigan, United States

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Minneapolis, Minnesota, United States

Site Status

Rochester, Minnesota, United States

Site Status

Haddon Heights, New Jersey, United States

Site Status

Newark, New Jersey, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Germantown, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

Site Status

Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

Site Status

Milwaukee, Wisconsin, United States

Site Status

Countries

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Canada United States

References

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Povsic TJ, Henry TD, Traverse JH, Fortuin FD, Schaer GL, Kereiakes DJ, Schatz RA, Zeiher AM, White CJ, Stewart DJ, Jolicoeur EM, Bass T, Henderson DA, Dignacco P, Gu Z, Al-Khalidi HR, Junge C, Nada A, Hunt AS, Losordo DW; RENEW Investigators. The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina. JACC Cardiovasc Interv. 2016 Aug 8;9(15):1576-85. doi: 10.1016/j.jcin.2016.05.003.

Reference Type DERIVED
PMID: 27491607 (View on PubMed)

Povsic TJ, Junge C, Nada A, Schatz RA, Harrington RA, Davidson CJ, Fortuin FD, Kereiakes DJ, Mendelsohn FO, Sherman W, Schaer GL, White CJ, Stewart D, Story K, Losordo DW, Henry TD. A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study. Am Heart J. 2013 Jun;165(6):854-861.e2. doi: 10.1016/j.ahj.2013.03.003. Epub 2013 Apr 19.

Reference Type DERIVED
PMID: 23708155 (View on PubMed)

Other Identifiers

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RENEW Study

Identifier Type: OTHER

Identifier Source: secondary_id

901001

Identifier Type: -

Identifier Source: org_study_id