AzTrials
AzTrials

Myocardial IschemiaPhase 2NCT00300053

ACT34-CMI -- Adult Autologous CD34+ Cells

A Phase 2 study testing CLBS14 (low-dose) and CLBS14 (high-dose) in people with Myocardial Ischemia, run by Lisata Therapeutics, Inc. at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 to 80 years
Conditions the study is for
Myocardial Ischemia
What is being tested?
CLBS14 (low-dose) and CLBS14 (high-dose)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
321 participants
Where
26 sitesUnited States
Study dates
Apr 2006to Mar 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • Saint Joseph's Research Institute

    Atlanta, Georgia, 30342

  • Cardiology PC

    Birmingham, Alabama, 35211

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Caritas Saint Elizabeth's Medical Center

    Boston, Massachusetts, 02135

  • Northwestern University Medical Center, Bluhm Cardiovascluar Institute

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • The Lindner Clinical Trial Center

    Cincinnati, Ohio, 45219

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • University of Florida Health Science Center

    Gainesville, Florida, 32610

  • University of Iowa Hospitals & Clinic

    Iowa City, Iowa, 52242

  • University of Florida Health Science Center

    Jacksonville, Florida, 32209

  • Scripps Memorial Hospital

    La Jolla, California, 92037

  • University of Wisconsin Medical School

    Madison, Wisconsin, 53792

  • Comprehensive Cardiovascular Care Group

    Milwaukee, Wisconsin, 53223

  • Abbott Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • New York Presbyterian Hospital - Columbia University Medical Center

    New York, New York, 10032

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

    New York, New York, 10065

  • Central Florida Cardiology Group

    Orlando, Florida, 32803

  • Arizona Heart Institute

    Phoenix, Arizona, 85005

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Swedish Heart & Vascular - Swedish Medical Center

    Seattle, Washington, 98122

  • Stanford University Hospital and Clinics

    Stanford, California, 94305

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

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)

The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.

Read the 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.

Being tested
CLBS14 (low-dose), CLBS14 (high-dose), placebo injection
Keywords
angina
Medical subject headings
Myocardial Ischemia, Angina Pectoris

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLBS14 (low-dose)Biological

    Also called G-CSF mobilized, autologous CD34+ cells

    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)Biological

    Also called G-CSF mobilized, autologous CD34+ cells

    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 injectionBiological

    Also called 0.9% NaCl (saline) in 5% autologous plasma

    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.

Study groups in NCT00300053
Study groupRoleWhat they receive
CLBS14: Low-Dose GroupExperimental10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10^5 (=100000) cells/kg bodyweight
Receives: Biological: CLBS14 (low-dose)
CLBS14: High-Dose GroupExperimental10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10^5 (=500000) cells/kg bodyweight
Receives: Biological: CLBS14 (high-dose)
Placebo injectionPlacebo comparator10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
Receives: Biological: placebo injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 and 12 months

Secondary outcomes (5)

  1. Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise

    A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.

    Measured: Change from Baseline to 6 months and change from baseline to 12 months after treatment

  2. Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels

    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

    Measured: Baseline and 12 months after treatment

  3. Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months

    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.

    Measured: Baseline to 6 months after treatment

  4. Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters

    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.

    Measured: Baseline to 6 months after treatment

  5. Change in Anti-anginal Medication (ie, Nitroglycerin) Use

    The mean nitroglycerin use per week was analyzed at baseline and 6 months

    Measured: Baseline to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionMar 2008
  4. Study completionMar 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
321 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00300053
Sponsor's protocol ID
24779
Status last verified
Jan 2021
First submitted
6 Mar 2006
Last updated
26 Jan 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21737787

  • 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.

    PubMed 27151378

  • 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.

    PubMed 23137499

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CLBS14 (low-dose) and CLBS14 (high-dose) in people with Myocardial Ischemia, run by Lisata Therapeutics, Inc. at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Angina Episodes Per Week at 6 and 12 Months (time frame: 6 and 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00300053, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in