AzTrials
AzTrials

Cardiomyopathy Due to AnthracyclinesPhase 1SENECANCT02509156

Stem Cell Injection in Cancer Survivors

A Phase 1 study testing Allo-MSCs in people with Cardiomyopathy Due to Anthracyclines, run by The University of Texas Health Science Center, Houston at 7 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 primary purpose of this study is to examine the safety and feasibility of delivering allogeneic human mesenchymal stem cells (allo-MSCs) by transendocardial injection to cancer survivors with left ventricular (LV) dysfunction secondary to anthracycline-induced cardiomyopathy (AIC). Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Cardiomyopathy Due to Anthracyclines
What is being tested?
Allo-MSCs
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
7 sitesUnited States
Study dates
Aug 2016to 20 Apr 2020
Phase
Phase 1
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 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To participate, a subject MUST:
  • Be ≥ 18 and < 80 years of age
  • Be a cancer survivor with diagnosis of AIC
  • Have an LVEF ≤ 45% by cMRI
  • Be in NYHA class II-III
  • Have received the initial diagnosis of AIC at least six months earlier and be on stable, optimally-tolerated therapy with beta-blockers, ACE inhibitors/ARBs, and/or aldosterone antagonists for 3 months, unless contraindicated
  • Have a period of at least two years of clinical cancer-free state* and low likelihood of recurrence (a five-year risk of recurrence estimated at 30% or less), as determined by an oncologist, based on tumor type, response to therapy, and negative metastatic work-up at the time of diagnosis (*exceptions to this are carcinoma in situ or fully resected basal and squamous cell cancer of the skin.)
  • Be a candidate for cardiac catheterization

Who cannot join

  • To participate, a subject MUST NOT HAVE:
  • A life expectancy <12 months
  • A CT scan or baseline cardiac MRI showing new tumor or suspicious lymphadenopathy raising concern of malignancy
  • Presence of obstructive CAD as determined via imaging within 5 years prior to study enrollment provided there have been no symptoms or evidence of CAD since the test
  • Had a previous myocardial infarction
  • A history of radiation therapy AND evidence of constrictive physiology and/or evidence of other patterns of non-ischemic cardiomyopathy on cardiac MRI (e.g., amyloidosis, sarcoidosis, hemochromatosis, pure radiation-induced cardiomyopathy, etc.) not consistent with AIC being the dominant etiology of heart failure
Show all 39Show fewer
  • Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent.
  • Aortic stenosis with valve area ≤ 1.5cm2
  • A history of LV reduction surgery or cardiomyoplasty
  • Evidence of cardiogenic shock
  • A history of ischemic or hemorrhagic stroke within 90 days of baseline testing
  • Liver dysfunction during baseline testing, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal
  • Diabetes with poorly controlled blood glucose levels (HbA1c > 8.5%)
  • An underlying autoimmune disorder or current immunosuppressive therapy (e.g., chronic corticosteroid, rheumatologic or immune modulating therapy) or likelihood of use of immunosuppressive therapy during participation in the trial (medications will be considered on a case by case basis)
  • A baseline eGFR <35 ml/min/1.73m2
  • A contrast allergy that cannot adequately be managed by premedication
  • Received gene or cell-based therapy from any source within the previous 12 months
  • A hematologic abnormality during baseline testing as evidenced by hemoglobin < 9 g/dl; hematocrit < 30%; absolute neutrophil count < 2,000 or total WBC count more than 2 times upper limit of normal; or platelet values < 100,000/ul
  • Evidence of active systemic infection at time of study product delivery
  • HIV and/or active HBV or HCV
  • Coagulopathy (INR > 1.5) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors) (see Section 6.4 re: injection procedure and anticoagulation therapy) Note: Subjects who cannot be withdrawn from anticoagulation will be excluded.
  • Presence of LV thrombus
  • Presence of a pacemaker and/or ICD generator with any of the following limitations/conditions:
  • manufactured before the year 2000
  • leads implanted < 6 weeks prior to consent
  • non-transvenous epicardial or abandoned leads
  • subcutaneous ICDs
  • leadless pacemakers
  • any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated
  • Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
  • A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to consent
  • Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
  • An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
  • Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
  • A history of drug abuse (use of illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
  • Cognitive or language barriers that prohibit obtaining informed consent or any study elements (interpreter permitted)
  • Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell based therapies) or device trial
  • Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation
  • Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Florida-Department of Medicine

    Gainesville, Florida, 32610

  • Texas Heart Institute

    Houston, Texas, 77030

  • Indiana Center for Vascular Biology and Medicine

    Indianapolis, Indiana, 46202

  • University of Louisville

    Louisville, Kentucky, 40202

  • University of Miami-Interdiciplinary Stem Cell Institute

    Miami, Florida, 33101

  • Minneapolis Heart Institute Foundation

    Minneapolis, Minnesota, 55407

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase I, First-in-Human, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Allogeneic Mesenchymal Stem Cells in Cancer Survivors With Anthracycline-Induced Cardiomyopathy

The primary purpose of this study is to examine the safety and feasibility of delivering allogeneic human mesenchymal stem cells (allo-MSCs) by transendocardial injection to cancer survivors with left ventricular (LV) dysfunction secondary to anthracycline-induced cardiomyopathy (AIC).

The secondary purpose of this study is to obtain preliminary evidence for therapeutic efficacy of allo-MSCs delivered by transendocardial injection to cancer survivors with LV dysfunction secondary to AIC.

Read the detailed description

This phase I, randomized, placebo-controlled, trial will evaluate the safety and feasibility of allo-MSCs administered by transendocardial injection in thirty-seven subjects with anthracycline-induced cardiomyopathy (AIC). The first six subjects received allo-MSC therapy (open label) and were assessed for safety and feasibility of the study procedures. Following 1 month data review of each of the six subjects by the National Heart, Lung, and Blood Institute Gene and Cell Therapy Data Safety Monitoring Board; this was followed by a randomized, double-blind clinical trial enrolling thirty-one subjects. These subjects were randomized 1:1 to receive allo-MSCs or placebo. All subjects underwent cardiac catheterization and study product administration using the NOGA Myostar catheter injection system. Subjects are being followed at 1 day, 1 week, 1 month, 6 months, and 12 months post study product injection. All endpoints are assessed at the 6 and 12 month visits which will occur 180 ±30 days and 365 ±30 days, respectively, after the day of study product injection (Day 0). For the purpose of the safety evaluations and endpoint analysis, the Investigators will utilize an "intention-to-treat" study population. In addition, because this phase I study is the first cell therapy study in this population, at 12 months available standard-of-care medical records for cancer surveillance will be reviewed for cancer recurrence.

Being tested
Allo-MSCs, Placebo
Keywords
Cardiomyopathy, AIC, Anthracyclines, Chemotherapy, Allogeneic, Mesenchymal stem cells, MSCs, Cancer survivors, Breast Cancer, Leukemia, Lymphoma, Sarcoma
Medical subject headings
Cardiomyopathies, Breast Neoplasms, Leukemia, Lymphoma, Sarcoma

What participants receive

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

  • Allo-MSCsBiological

    Also called Allogeneic Mesenchymal Stem Cells

    20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

  • PlaceboBiological

    Also called Buminate solution

    20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Study groups in NCT02509156
Study groupRoleWhat they receive
Allo-MSCsExperimentalTarget dose of 100 million allo-MSCs
Receives: Biological: Allo-MSCs
PlaceboPlacebo comparatorBuminate solution
Receives: Biological: Placebo

What is being measured

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

  1. Proportion of Major Adverse Cardiac Events (MACE)

    Proportion of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).

    Measured: Baseline to 12 months

  2. Proportion of Other Significant Clinical Events

    Proportion of other significant adjudicated clinical events including: non-fatal stroke, non-fatal MI, coronary artery revascularization, ventricular tachycardia/fibrillation, pericardial tamponade, infectious myocarditis, hypersensitivity reaction, neoplasm, and/or other potential deleterious late effects.

    Measured: Baseline to 12 months

  3. Subjects With Events Precluding Their Receipt of Product

    Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product.

    Measured: Randomization to SPI

  4. Subjects Who Receive Less Than 20 Injections During SPI

    Number and percent of subjects who receive less than 20 injections during SPI

    Measured: During SPI procedure

  5. Subjects Who Did Not Receive the Study Product (Either 100 Million Cells or Placebo)

    Number and percent of subjects who did not receive the study product (either 100 million cells or placebo)

    Measured: During SPI procedure

  6. Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable

    Number and percent of subjects who have at least one cardiac MRI endpoint measure that is uninterpretable due to issues related to the device, including, but not limited to, inability to undergo the procedure.

    Measured: Baseline to 12 months

  7. Subjects Who Fail to Complete Follow-up

    Number and percent of subjects who fail to complete follow up

    Measured: Baseline to 12 months

Secondary outcomes (21)

  1. Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

    Change in left ventricular ejection fraction as assessed via cardiac MRI.

    Measured: Baseline to 12 months

  2. Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  3. Change From Baseline in Global Strain (HARP MRI)

    Change in global circumferential strain as assessed via cardiac MRI

    Measured: Baseline to 12 months

  4. Change From Baseline in Global Strain (HARP MRI)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  5. Change From Baseline in Regional Strain (HARP MRI)

    Change in regional longitudinal strain as assessed via cardiac MRI

    Measured: Baseline to 12 months

  6. Change From Baseline in Regional Strain (HARP MRI)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  7. Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)

    Change in left ventricular end diastolic volume index as measured via cardiac MRI

    Measured: Baseline to 12 months

  8. Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  9. Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)

    Change in left ventricular end systolic volume index as assessed via cardiac MRI

    Measured: Baseline to 12 months

  10. Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  11. Change From Baseline in Left Ventricular Sphericity Index

    Change in Left Ventricular Sphericity Index as assessed by cardiac MRI. Sphericity index is the ratio of the long and short axis measurements of the left ventricle.

    Measured: Baseline to 12 months

  12. Change From Baseline in Left Ventricular Sphericity Index-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Sphericity index is the ratio of the long and short axis measurements of the left ventricle.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  13. Change From Baseline in Area of Injury

    Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.

    Measured: Baseline to 12 months

  14. Change From Baseline in Area of Injury-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  15. Change From Baseline in Exercise Tolerance (Six Minute Walk Test)

    Change in the distance walked (in meters) as measured by the six minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 min). The average distance of the two walk tests will be used for analysis.

    Measured: Baseline to 12 months

  16. Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory

    Change in the distance walked (in feet) as measured by the six minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 min). The average distance of the two walk tests will be used for analysis. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  17. Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score

    Change in the quality of life summary score as measured by the Minnesota Living with Heart Failure Questionnaire. Minimum and maximum scores for scale are 0 and 105 respectively. Lower scores indicative of better outcome.

    Measured: Baseline to 12 months

  18. Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Minimum and maximum scores for scale are 0 and 105 respectively. Lower scores indicative of better outcome.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  19. Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)

    Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw

    Measured: Baseline to 12 months

  20. Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory

    The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). If there is no interaction between change over time and treatment a single calculated value is the slope (the change per six months) from the model. If there is an interaction, the p-value for interaction is presented along with two calculated values representing the slope (the change per six months) for each treatment arm from the model.

    Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)

  21. Cumulative Days Alive and Out of Hospital for Heart Failure

    Days alive and out of hospital for heart failure during the study evaluation period. Subjects were allotted a visit window extending 30 days past their anticipated 12-month visit (i.e., 395 days).

    Measured: Baseline to End of 12 Month Visit Window (i.e. 395 days after intervention)

Timeline

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

  1. First posted27 Jul 2015 (estimated)
  2. Study startAug 2016
  3. Primary completionNov 2019
  4. Study completion20 Apr 2020

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02509156
Sponsor's protocol ID
HSC-SPH-15-0443
Other IDs
5UM1HL087318
Acronym
SENECA
Status last verified
Oct 2020
First submitted
23 Jul 2015
Last updated
5 Nov 2020
Data monitoring committee
Yes

Publications

  • Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, Williams K, Itescu S, Sanders P, Gronthos S, Zannettino AC, Worthley SG. Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC Cardiovasc Interv. 2010 Sep;3(9):974-83. doi: 10.1016/j.jcin.2010.05.016.

    PubMed 20850099

  • Nazarian S, Halperin HR. How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm. 2009 Jan;6(1):138-43. doi: 10.1016/j.hrthm.2008.10.021. Epub 2008 Oct 22. No abstract available.

    PubMed 19121814

  • Bolli R, Hare JM, Henry TD, Lenneman CG, March KL, Miller K, Pepine CJ, Perin EC, Traverse JH, Willerson JT, Yang PC, Gee AP, Lima JA, Moye L, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. Am Heart J. 2018 Jul;201:54-62. doi: 10.1016/j.ahj.2018.02.009. Epub 2018 Apr 4.

    PubMed 29910056

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allo-MSCs in people with Cardiomyopathy Due to Anthracyclines, run by The University of Texas Health Science Center, Houston at 7 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 8 inclusion and 39 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 5 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 5 Nov 2020). 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?

Proportion of Major Adverse Cardiac Events (MACE) (time frame: Baseline to 12 months). The study lists 7 primary outcomes in all. 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 NCT02509156, 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 5 Nov 2020.

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