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Stem Cell Injection in Cancer Survivors (SENECA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by The University of Texas Health Science Center, Houston
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Dr Lemuel A Moye III, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT02509156
First received: July 23, 2015
Last updated: March 3, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
Cardiomyopathy Due to Anthracyclines
Biological: Allo-MSCs
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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 ]

Estimated Enrollment: 36
Study Start Date: August 2016
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allo-MSCs
Target dose of 100 million allo-MSCs
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
Placebo Comparator: Placebo
Buminate solution
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

Detailed Description:

This phase I, randomized, placebo-controlled, trial will evaluate the safety and feasibility of allo-MSCs administered by transendocardial injection in thirty-six subjects with anthracycline-induced cardiomyopathy (AIC). The first six subjects will receive allo-MSC therapy (open label) and will be 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 will be followed by a randomized, double-blind clinical trial enrolling thirty subjects. These thirty subjects will be randomized 1:1 to receive allo-MSCs or placebo. All subjects will undergo cardiac catheterization and study product administration using the NOGA Myostar catheter injection system. Subjects will be followed at 1 day, 1 week, 1 month, 6 months, and 12 months post study product injection. All endpoints will be 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 all available standard-of-care medical records for cancer surveillance will be reviewed for cancer recurrence.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≤ 40% 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 1 month, 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 CAD as determined via imaging within 12 months prior study enrollment (e.g. a rest and stress nuclear scan (SPECT/PET/CT), a stress echocardiogram, stress MRI, or cardiac computed tomography angiography (CCTA). If coronary arteriogram, within the last 24 months)
  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
  14. A baseline eGFR <35 ml/min/1.73m2
  15. A contrast allergy that cannot adequately be managed by premedication
  16. A history of organ or cell transplantation, except for transplantation of bone, skin, ligament, tendon, or cornea
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02509156

Contacts
Contact: Shelly L Sayre, MPH 713-500-9529 Shelly.L.Sayre@uth.tmc.edu
Contact: Lemuel A Moye, MD, PhD 713-500-9518 lemmoye@msn.com

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Fouzia Khan    650-736-1410    fouziak@stanford.edu   
Principal Investigator: Phil Yang, MD         
United States, Florida
University of Florida-Department of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Sarah Long    352-273-8932    Sarah.Long@medicine.ufl.edu   
Contact: Nicole Bostick    352-273-8938    Janette.Bostick@medicine.ufl.edu   
Principal Investigator: Carl Pepine, MD         
University of Miami-Interdiciplinary Stem Cell Institute Recruiting
Miami, Florida, United States, 33101
Contact: Cindy Delgado    305-243-1152    cdelgado5@med.miami.edu   
Contact: Jairo Tovar    305-243-5399    JAT243@med.miami.edu   
Principal Investigator: Raul Mitrani, MD         
United States, Indiana
Indiana Center for Vascular Biology and Medicine Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Alicia Limbach    317-278-6585    aglimbac@iu.edu   
Contact: Ashley Vetor    317-274-0858    abozell@iu.edu   
Principal Investigator: J. Emanuel Finet, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Shari Williams    502-407-3259    shari.williams@louisville.edu   
Contact: Heidi Wilson    502-540-3721    heidi.wilson@louisville.edu   
Principal Investigator: Roberto Bolli, MD         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Jane Fox    612-863-6289    Jane.fox@allina.com   
Contact: Patti Mitchell    612-863-6287    patricia.mitchell@allina.com   
Principal Investigator: Jay Traverse, MD         
United States, Texas
Texas Heart Institute Recruiting
Houston, Texas, United States, 77030
Contact: Nichole Piece    832-355-9173    npiece@texasheart.org   
Contact: Sara Sampaio       ssampaio@texasheart.org   
Principal Investigator: James Willerson, MD         
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Study Chair: Robert Simari, MD CCTRN Steering Committee Chair
  More Information

Additional Information:
Publications:
Responsible Party: Dr Lemuel A Moye III, Professor of Biostatistics, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02509156     History of Changes
Other Study ID Numbers: HSC-SPH-15-0443
5UM1HL087318 ( US NIH Grant/Contract Award Number )
Study First Received: July 23, 2015
Last Updated: March 3, 2017

Keywords provided by The University of Texas Health Science Center, Houston:
Cardiomyopathy
AIC
Anthracyclines
Chemotherapy
Allogeneic
Mesenchymal stem cells
MSCs
Cancer survivors
Breast Cancer
Leukemia
Lymphoma
Sarcoma

Additional relevant MeSH terms:
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 24, 2017