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Trial record 4 of 415 for:    SENECA

Stem Cell Injection in Cancer Survivors (SENECA)

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ClinicalTrials.gov Identifier: NCT02509156
Recruitment Status : Active, not recruiting
First Posted : July 27, 2015
Last Update Posted : October 31, 2018
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

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.


Condition or disease Intervention/treatment Phase
Cardiomyopathy Due to Anthracyclines Biological: Allo-MSCs Biological: Placebo Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (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
Actual Study Start Date : August 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  2. Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  3. Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  4. Change in Left Ventricular End Diastolic Volume Index (LVEDVI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  5. Change in Left Ventricular End Systolic Volume Index (LVESVI) as measured by cMRI [ Time Frame: Baseline to 12 months ]
  6. Change in Left Ventricular Sphericity Index as measured by cMRI [ Time Frame: Baseline to 12 months ]
  7. Change in Area of Injury as measured by cMRI [ Time Frame: Baseline to 12 months ]
    Inflammation, edema, fibrosis

  8. Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: Baseline to 12 months ]
  9. Change in Minnesota Living with Heart Failure Questionnaire (MHLFQ) Score [ Time Frame: Baseline to 12 months ]
  10. Cumulative Days Alive and Out of the Hospital [ Time Frame: Baseline to 12 months ]
  11. Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: Baseline to 12 months ]
  12. Incidence rate of Death [ Time Frame: Baseline to 12 months ]
  13. Incidence rate of Hospitalization for Heart Failure [ Time Frame: Baseline to 12 months ]
  14. Incidence rate of Exacerbation of Heart Failure (Non hospitalization) [ Time Frame: Baseline to 12 months ]

Other Outcome Measures:
  1. Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  2. Change in Global Strain (HARP MRI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  3. Change in Regional Strain (HARP MRI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  4. Change in Left Ventricular End Diastolic Volume Index (LVEDVI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  5. Change in Left Ventricular End Systolic Volume Index (LVESVI) as measured by cMRI [ Time Frame: 6 months to 12 months ]
  6. Change in Left Ventricular Sphericity Index as measured by cMRI [ Time Frame: 6 months to 12 months ]
  7. Change in Area of Injury as measured by cMRI [ Time Frame: 6 months to 12 months ]
    Inflammation, edema, fibrosis

  8. Change in Exercise Tolerance as measured by the six minute walk test [ Time Frame: 6 months to 12 months ]
  9. Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score [ Time Frame: 6 months to 12 months ]
  10. The difference in the Cumulative Days Alive and Out of Hospital [ Time Frame: 6 months to 12 months ]
  11. Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw [ Time Frame: 6 months to 12 months ]
  12. Incidence rate of Death [ Time Frame: 6 months to 12 months ]
  13. Incidence rate of Hospitalization for Heart Failure [ Time Frame: 6 months to 12 months ]
  14. Incidence rate of Heart Failure Exacerbation (Non hospitalization) [ Time Frame: 6 months to 12 months ]


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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
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 ≤ 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02509156


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Florida
University of Florida-Department of Medicine
Gainesville, Florida, United States, 32610
University of Miami-Interdiciplinary Stem Cell Institute
Miami, Florida, United States, 33101
United States, Indiana
Indiana Center for Vascular Biology and Medicine
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, Texas
Texas Heart Institute
Houston, Texas, United States, 77030
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

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 ( U.S. NIH Grant/Contract )
First Posted: July 27, 2015    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018

Keywords provided by Dr Lemuel A Moye III, 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