Stem Cell Injection in Cancer Survivors
Condition: Cardiomyopathy Due to Anthracyclines
MeSH terms: Cardiomyopathies
Intervention: Allo-MSCs; Placebo
Intervention description: 20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure); 20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Cardiomyopathy; AIC; Anthracyclines; Chemotherapy; Allogeneic; Mesenchymal stem cells; MSCs; Cancer survivors; Breast Cancer; Leukemia; Lymphoma; Sarcoma

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.
    

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 ≤ 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