Stem Cell Injection in Cancer Survivors

NCT ID: NCT02509156

Last Updated: 2020-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2020-04-20

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.

Detailed Description

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

Conditions

Cardiomyopathy Due to Anthracyclines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Allo-MSCs

Target dose of 100 million allo-MSCs

Group Type: EXPERIMENTAL

Allo-MSCs

Intervention Type: BIOLOGICAL

20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Placebo

Buminate solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Interventions

Allo-MSCs

20 transendocardial injections of 0.4ml allo-MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Intervention Type: BIOLOGICAL

Placebo

20 transendocardial injections of 0.4ml Buminate solution administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Intervention Type: BIOLOGICAL

Other Intervention Names

Allogeneic Mesenchymal Stem Cells; Buminate 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 ≤ 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Barry R Davis

Professor of Biostatistics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Simari, MD

Role: STUDY_CHAIR

CCTRN Steering Committee Chair

Locations

Stanford University School of Medicine

Stanford, California, United States

University of Florida-Department of Medicine

Gainesville, Florida, United States

University of Miami-Interdiciplinary Stem Cell Institute

Miami, Florida, United States

Indiana Center for Vascular Biology and Medicine

Indianapolis, Indiana, United States

University of Louisville

Louisville, Kentucky, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Texas Heart Institute

Houston, Texas, United States

Countries

United States

References

Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, Williams K, Itescu S, Sanders P, Gronthos S, Zannettino AC, Worthley SG. Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC Cardiovasc Interv. 2010 Sep;3(9):974-83. doi: 10.1016/j.jcin.2010.05.016.

Reference Type: BACKGROUND

PMID: 20850099 (View on PubMed)

Nazarian S, Halperin HR. How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm. 2009 Jan;6(1):138-43. doi: 10.1016/j.hrthm.2008.10.021. Epub 2008 Oct 22. No abstract available.

Reference Type: BACKGROUND

PMID: 19121814 (View on PubMed)

Bolli R, Hare JM, Henry TD, Lenneman CG, March KL, Miller K, Pepine CJ, Perin EC, Traverse JH, Willerson JT, Yang PC, Gee AP, Lima JA, Moye L, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial. Am Heart J. 2018 Jul;201:54-62. doi: 10.1016/j.ahj.2018.02.009. Epub 2018 Apr 4.

Reference Type: BACKGROUND

PMID: 29910056 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.cctrn.org

Cardiovascular Cell Therapy Research Network

http://www.nhlbi.nih.gov

National Heart, Lung, and Blood Institute

Other Identifiers

5UM1HL087318

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-SPH-15-0443

Identifier Type: -

Identifier Source: org_study_id