A Study to Assess the Effect of Intravenous Dose of (aMBMC) to Subjects With Non-ischemic Heart Failure
Condition: Non-Ischemic Heart Failure
MeSH terms: Heart Failure
Intervention: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC); Lactated Ringer's Solution
Intervention description: One time infusion Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg.; One time infusion 1.5mL/kg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-ischemic Heart Failure; Stem Cells

Summary:

      A phase IIa study to assess the safety and preliminary efficacy of intravenous dose of
      ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells in subjects with non-ischemic
      heart failure.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females ≥18 years of age

          2. LVEF ≤35% on echocardiogram within 12 months of randomization to undergo MRI

          3. Screening cardiac MRI at baseline with:

             Ejection fraction ≤40% No significant hyper enhancement on MRI scan in the opinion of
             the central imaging lab reviewer

          4. Patients with non-ischemic heart failure etiology, as documented by absent or
             non-obstructive coronary artery disease on x-ray angiography or coronary computed
             tomography

          5. Patients with history of heart failure and treated for at least three months with GDMT

          6. NYHA class II-III symptoms

          7. Ability to understand and provide signed informed consent

          8. Reasonable expectation that patient will receive standard post-treatment care and
             attend all scheduled safety follow-up visits

        Exclusion Criteria:

          1. Pregnant or nursing women or those of childbearing age and not using an effective
             method of contraception

          2. History of stroke within 3 months

          3. Cardiac surgery within 3 months prior to randomization or the likelihood of a
             requirement for such procedures during the study period

          4. Current ICD or CRT or implantation planned within 6 months of infusion

          5. Presence of clinically significant, uncorrected valvular heart disease, hypertrophic
             or restrictive cardiomyopathy, active myocarditis, or uncontrolled hypertension

          6. History of cardiac arrest or life-threatening arrhythmias within 3 months

          7. Treatment with parenteral inotropic agents within 1 month of randomization

          8. Anticipated cardiac transplantation within 1 year

          9. Illness other than heart failure with life expectancy less than 1 year

         10. Received an experimental drug or device within 30 days of randomization

         11. Left ventricular assist device or implantation planned in the next 6 months

         12. Patients with complex congenital heart disease

         13. Uncontrolled seizure disorder

         14. Presence of immune deficiency

         15. Clinically significant hematologic, hepatic, or renal impairment as determined by
             screening clinical laboratory tests:

               -  Liver disease = ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x
                  normal)

               -  Renal disease = estimated glomerular filtration rate as assessed by the MDRD
                  formula <30 ml/min

               -  Hematologic = Unexplained leukocytosis >10 or hemoglobin < 9gm/dl

         16. Presence of any other clinically-significant medical condition, psychiatric condition,
             or laboratory abnormality, that in the judgment of the investigator or sponsor for
             which participation in the study would pose a safety risk to the subject

         17. Inability to comply with the conditions of the protocol

         18. Malignancy within the previous five years, except adequately treated basal cell
             carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in
             situ of the cervix

         19. Active myocarditis or early postpartum cardiomyopathy (within six months).

         20. Systemic corticosteroids, cytostatics, immunosuppressive drug therapy
             (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting
             or cytotoxic drugs taken within four weeks prior to study treatment

         21. Porphyria

         22. Allergy to sodium citrate or any "caine" type of local anesthetic

         23. Any contraindication for gadolinium use for MRI

         24. Patient scheduled for hospice care

         25. Clinically relevant abnormal findings in the clinical history, physical examination,
             ECG, or laboratory tests at the screening assessment that would interfere with the
             objectives of the study or would preclude safe completion of the study. Abnormal
             findings could include: known HIV infection or other immunodeficiency state, chronic
             active viral infection (such as hepatitis B or C), acute systemic infections (defined
             as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding,
             or any severe or acute concomitant illness or injury

         26. Any other medical, social, or geographical factor that would make it unlikely that the
             patient could comply with study procedures (e.g., alcohol abuse, lack of permanent
             residence, severe depression, disorientation, distant location, or noncompliance)