Stem Cell Injection in Cancer Survivors

Not Recruiting

Trial ID: NCT02509156


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.

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

Stanford Investigator(s)

Phillip C. Yang, MD
Phillip C. Yang, MD

Professor of Medicine (Cardiovascular Medicine)


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

      - 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


biological: Allo-MSCs

biological: Placebo

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Fouzia Khan