Clinical Trials /

Stem Cell Injection in Cancer Survivors

NCT02509156

Description:

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.

Related Conditions:
  • Cancer
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stem Cell Injection in Cancer Survivors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: HSC-SPH-15-0443
  • SECONDARY ID: 5UM1HL087318
  • NCT ID: NCT02509156

Conditions

  • Cardiomyopathy Due to Anthracyclines

Interventions

DrugSynonymsArms
Allo-MSCsAllogeneic Mesenchymal Stem CellsAllo-MSCs
PlaceboBuminate solutionPlacebo

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Allo-MSCsExperimentalTarget dose of 100 million allo-MSCs
    PlaceboPlacebo ComparatorBuminate solution

      Eligibility 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
            
      Maximum Eligible Age:79 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI
      Time Frame:Baseline to 12 months
      Safety Issue:
      Description:Inflammation, edema, fibrosis

      Secondary Outcome Measures

      Measure:Change in Left Ventricular Ejection Fraction (LVEF) as measured by cMRI
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Global Strain (HARP MRI) as measured by cMRI
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Regional Strain (HARP MRI) as measured by cMRI
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Left Ventricular End Diastolic Volume Index (LVEDVI)
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Left Ventricular End Systolic Volume Index (LVESVI)
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Lef Ventricular Sphericity Index as measured by cMRI
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Area of Injury as measured by cMRI
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:Inflammation, edema, fibrosis
      Measure:Change in Exercise Tolerance as measured by the six minute walk test
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Incidence Rate of Major Cardiac Adverse Events (MACE)
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Cumulative Days Alive and Out of Hospital
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:
      Measure:Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured by blood draw
      Time Frame:Baseline to 6 months
      Safety Issue:
      Description:

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:The University of Texas Health Science Center, Houston

      Trial Keywords

      • Cardiomyopathy
      • AIC
      • Anthracyclines
      • Chemotherapy
      • Allogeneic
      • Mesenchymal stem cells
      • MSCs
      • Cancer survivors
      • Breast Cancer
      • Leukemia
      • Lymphoma
      • Sarcoma

      Last Updated

      March 3, 2017