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Stem Cell Injection in Cancer Survivors (SENECA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02509156
Recruitment Status : Active, not recruiting
First Posted : July 27, 2015
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Barry R Davis, The University of Texas Health Science Center, Houston

Tracking Information
First Submitted Date  ICMJE July 23, 2015
First Posted Date  ICMJE July 27, 2015
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE August 2016
Actual Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • Incidence of major adverse cardiac events (MACE) [ Time Frame: Baseline to 6 months ]
    Incidence of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
  • Incidence of major adverse cardiac events (MACE) [ Time Frame: Baseline to 12 months ]
    Incidence of adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
  • Incidence of other significant clinical events [ Time Frame: Baseline to 6 months ]
    Incidence 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.
  • Incidence of other significant clinical events [ Time Frame: Baseline to 12 months ]
    Incidence 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.
  • Subjects with events precluding their receipt of product [ Time Frame: Randomization to SPI ]
    Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product.
  • Subjects who receive less than 20 injections during SPI [ Time Frame: During SPI procedure ]
    Number and percent of subjects who receive less than 20 injections during SPI
  • Subjects who did not receive the intended dose of cells [ Time Frame: During SPI procedure ]
    Number and percent of subjects who did not receive the intended dose of cells(100 million)
  • Subjects who have at least one cardiac MRI endpoint measure that is uninterpretable [ Time Frame: Baseline to 12 months ]
    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.
  • Subjects who fail to complete follow-up [ Time Frame: Baseline to 12 months ]
    Number and percent of subjects who fail to complete follow up
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Left Ventricular End Diastolic Volume Index (LVEDVI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Left Ventricular End Systolic Volume Index (LVESVI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Left Ventricular Sphericity Index as measured by cMRI [ Time Frame: Baseline to 12 months ]
  • Change in Area of Injury as measured by cMRI [ Time Frame: Baseline to 12 months ]
    Inflammation, edema, fibrosis
  • Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: Baseline to 12 months ]
  • Change in Minnesota Living with Heart Failure Questionnaire (MHLFQ) Score [ Time Frame: Baseline to 12 months ]
  • Incidence Rate of Major Adverse Cardiac Events (MACE) [ Time Frame: Baseline to 12 months ]
  • Cumulative Days Alive and Out of the Hospital [ Time Frame: Baseline to 12 months ]
  • Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: Baseline to 12 months ]
Change History Complete list of historical versions of study NCT02509156 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in left ventricular ejection fraction as assessed via cardiac MRI.
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline to 6 months ]
    Change in left ventricular ejection fraction as assessed via cardiac MRI.
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline to 12 months ]
    Change in left ventricular ejection fraction as assessed via cardiac MRI.
  • Global Strain (HARP MRI) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in global circumferential strain as assessed via cardiac MRI
  • Global Strain (HARP MRI) [ Time Frame: Baseline to 6 months ]
    Change in global circumferential strain as assessed via cardiac MRI
  • Global Strain (HARP MRI) [ Time Frame: Baseline to 12 months ]
    Change in global circumferential strain as assessed via cardiac MRI
  • Regional Strain (HARP MRI) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in regional longitudinal strain as assessed via cardiac MRI
  • Regional Strain (HARP MRI) [ Time Frame: Baseline to 6 months ]
    Change in regional longitudinal strain as assessed via cardiac MRI
  • Regional Strain (HARP MRI) [ Time Frame: Baseline to 12 months ]
    Change in regional longitudinal strain as assessed via cardiac MRI
  • Left Ventricular End Diastolic Volume Index (LVEDVI) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in left ventricular end diastolic volume index as measured via cardiac MRI
  • Left Ventricular End Diastolic Volume Index (LVEDVI) [ Time Frame: Baseline to 6 months ]
    Change in left ventricular end diastolic volume index as measured via cardiac MRI
  • Left Ventricular End Diastolic Volume Index (LVEDVI) [ Time Frame: Baseline to 12 months ]
    Change in left ventricular end diastolic volume index as measured via cardiac MRI
  • Left Ventricular End Systolic Volume Index (LVESVI) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in left ventricular end systolic volume index as assessed via cardiac MRI
  • Left Ventricular End Systolic Volume Index (LVESVI) [ Time Frame: Baseline to 6 months ]
    Change in left ventricular end systolic volume index as assessed via cardiac MRI
  • Left Ventricular End Systolic Volume Index (LVESVI) [ Time Frame: Baseline to 12 months ]
    Change in left ventricular end systolic volume index as assessed via cardiac MRI
  • Left Ventricular Sphericity Index [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    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.
  • Left Ventricular Sphericity Index [ Time Frame: Baseline to 6 months ]
    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.
  • Left Ventricular Sphericity Index [ Time Frame: Baseline to 12 months ]
    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.
  • Area of Injury [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.
  • Area of Injury [ Time Frame: Baseline to 6 months ]
    Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.
  • Area of Injury [ Time Frame: Baseline to 12 months ]
    Change in the scar percent (scar mass normalized to left ventricular mass) as assessed via cardiac MRI.
  • Exercise Tolerance (Six Minute Walk test) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    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.
  • Exercise Tolerance (Six Minute Walk test) [ Time Frame: Baseline to 6 months ]
    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.
  • Exercise Tolerance (Six Minute Walk test) [ Time Frame: Baseline to 12 months ]
    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.
  • Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in the quality of life questionnaire score as measured by the MLHFQ.
  • Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: Baseline to 6 months ]
    Change in the quality of life questionnaire score as measured by the MLHFQ.
  • Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: Baseline to 12 months ]
    Change in the quality of life questionnaire score as measured by the MLHFQ.
  • N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Assessed as a trajectory (baseline, 6 months, and 12 months) ]
    Change in NT-proBNP as measured via blood draw
  • N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline to 6 months ]
    Change in NT-proBNP as measured via blood draw
  • N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline to 12 months ]
    Change in NT-proBNP as measured via blood draw
  • Cumulative Days Alive and Out of Hospital [ Time Frame: Baseline to 12 months ]
    Days alive and out of hospital during the study evaluation period
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  • Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  • Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 6 months ]
  • Change in Left Ventricular End Diastolic Volume Index (LVEDVI) [ Time Frame: Baseline to 6 months ]
  • Change in Left Ventricular End Systolic Volume Index (LVESVI) [ Time Frame: Baseline to 6 months ]
  • Change in Lef Ventricular Sphericity Index as measured by cMRI [ Time Frame: Baseline to 6 months ]
  • Change in Area of Injury as measured by cMRI [ Time Frame: Baseline to 6 months ]
    Inflammation, edema, fibrosis
  • Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: Baseline to 6 months ]
  • Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: Baseline to 6 months ]
  • Incidence Rate of Major Cardiac Adverse Events (MACE) [ Time Frame: Baseline to 6 months ]
  • Cumulative Days Alive and Out of Hospital [ Time Frame: Baseline to 6 months ]
  • Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: Baseline to 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: July 23, 2015)
  • Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Left Ventricular End Diastolic Volume Index (LVEDVI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Left Ventricular End Systolic Volume Index (LVESVI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Left Ventricular Sphericity Index as measured by cMRI [ Time Frame: 6 months to 12 months ]
  • Change in Area of Injury as measured by cMRI [ Time Frame: 6 months to 12 months ]
    Inflammation, edema, fibrosis
  • Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: 6 months to 12 months ]
  • Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: 6 months to 12 months ]
  • The difference in the Incident Rate of Major Adverse Cardiac Events (MACE) [ Time Frame: 6 months to 12 months ]
  • The difference in the Cumulative Days Alive and Out of Hospital [ Time Frame: 6 months to 12 months ]
  • Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: 6 months to 12 months ]
 
Descriptive Information
Brief Title  ICMJE Stem Cell Injection in Cancer Survivors
Official Title  ICMJE 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
Brief 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).

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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cardiomyopathy Due to Anthracyclines
Intervention  ICMJE
  • Biological: Allo-MSCs
    20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
    Other Name: Allogeneic Mesenchymal Stem Cells
  • Biological: Placebo
    20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
    Other Name: Buminate solution
Study Arms  ICMJE
  • Experimental: Allo-MSCs
    Target dose of 100 million allo-MSCs
    Intervention: Biological: Allo-MSCs
  • Placebo Comparator: Placebo
    Buminate solution
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 30, 2018)
37
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2015)
36
Estimated Study Completion Date  ICMJE May 2020
Actual Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

To participate, a subject MUST:

  1. Be ≥ 18 and < 80 years of age
  2. Be a cancer survivor with diagnosis of AIC
  3. Have an LVEF ≤ 45% by cMRI
  4. Be in NYHA class II-III
  5. 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
  6. 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.)
  7. Be a candidate for cardiac catheterization

Exclusion Criteria

To participate, a subject MUST NOT HAVE:

  1. A life expectancy <12 months
  2. A CT scan or baseline cardiac MRI showing new tumor or suspicious lymphadenopathy raising concern of malignancy
  3. 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
  4. Had a previous myocardial infarction
  5. 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
  6. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent.
  7. Aortic stenosis with valve area ≤ 1.5cm2
  8. A history of LV reduction surgery or cardiomyoplasty
  9. Evidence of cardiogenic shock
  10. A history of ischemic or hemorrhagic stroke within 90 days of baseline testing
  11. Liver dysfunction during baseline testing, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal
  12. Diabetes with poorly controlled blood glucose levels (HbA1c > 8.5%)
  13. 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)
  14. A baseline eGFR <35 ml/min/1.73m2
  15. A contrast allergy that cannot adequately be managed by premedication
  16. Received gene or cell-based therapy from any source within the previous 12 months
  17. 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
  18. Evidence of active systemic infection at time of study product delivery
  19. HIV and/or active HBV or HCV
  20. 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.
  21. Presence of LV thrombus
  22. 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
  23. Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
  24. A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to consent
  25. Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
  26. An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
  27. 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
  28. 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
  29. Cognitive or language barriers that prohibit obtaining informed consent or any study elements (interpreter permitted)
  30. Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell based therapies) or device trial
  31. Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation
  32. Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02509156
Other Study ID Numbers  ICMJE HSC-SPH-15-0443
5UM1HL087318 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Barry R Davis, The University of Texas Health Science Center, Houston
Study Sponsor  ICMJE The University of Texas Health Science Center, Houston
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Study Chair: Robert Simari, MD CCTRN Steering Committee Chair
PRS Account The University of Texas Health Science Center, Houston
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP