The study is a phase II single-centered, single group, prospective clinical trial to evaluate the safety of HMA-CD20 doses among stable patients with class III/IV according to the NYHA classification with HFrEF receiving standard of care therapy. The index qualifying HFrEF must have EF < 40% based on echocardiographic or cardiac MRI techniques, heart failure class III/IV according to the NYHA classification,aged 40-60 years, being diagnosed less than 12 months before enrollment of study, following the standard heart failure treatment regimen.

4.1 Inclusion criteria

1. Men and women (women not pregnant neither in lactation period) between ≥ 40 to 60 years-old.
2. Diagnosis of HFrEF and functional class III-IV.
3. EF ≤ 40% evaluated by MRI and or transthoracic echocardiography, with validity of twelve months.
4. Inadequate response to standard treatment.
5. Urgent medical attention or hospitalization due to worsening of HF or MI in the last 12 months.
6. Diagnosis of ischemic or non ischemic dilated cardiomyopathy.
7. Life expectancy of at least six months, in investigator opinion.
8. Participants should sign an (informed consent form) ICF form personally.

4.2 Exclusion criteria

1. Severe primary valvular cardiopathy or valvular prosthesis (mechanical or bio-valve).
2. History of heart transplant surgery, cardiomyoplasty, left ventricular reduction surgery, valvuloplasty, implantation of a ventricle assist device (VAD) and surgical cardiac congenital defect correction.
3. Uncontrolled atrial fibrillation (HR > 100 bpm), atrial flutter, sustained atrial fibrillation and / or significant arrhythmias such as sustained or unsustained ventricular tachychardia, bigeminy or trigeminy evidenced by Holter during the prescreening period.
4. Implantable cardioverter defibrillator (ICD) within the last three months.
5. Acute coronary syndromes that required pharmacological or mechanical reperfusion or medical treatment, within 30 days before selection.
6. Percutaneous coronary intervention within 30 days prior to selection.
7. Treatment with inotropic agents (dobutamine, milrinone, levosimendan), I.V. diuretics or vasodilators within 30 days of selection.
8. Pregnant women or breast feeding period without adequate prenatal care.
9. Untreated thyroid disease.
10. Patients with GFR <30mL/min based on the cockcroft-gualt formula
11. Rapidly progressive glomerulonephritis, seizures or psychosis, progressive neuropathy or myopathy.
12. Hemoglobin: < 8.5 mg/dL.
13. WBC count less than 5000/mm3
14. Platelets: <100,000/mm, AST or ALT >2.5 × upper limit of normal (ULN) unless related to primary disease.
15. Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody).
16. History of positive HIV.
17. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
18. Recipients of an available attenuated vaccine within four weeks prior to randomization.
19. Previous treatment with HMA-CD20 or any immunotherapy.
20. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
21. Known active bacterial, viral, fungal (excluding fungal infections of nail beds/onychomycosis), mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease) or any major episode of infection requiring hospitalization or treatment with I.V. antibiotics within four weeks of screening, or oral antibiotics within two weeks before screening.
22. Consistent steroid administration within the past four weeks.
23. Lack of peripheral venous access.
24. Concomitant or previous malignancies, except curatively resected non-melanoma skin carcinomas or carcinoma in situ of the cervix.
25. History of psychiatric disorder that would interfere with participation in this protocol, such as depression, bipolar syndrome, schizophrenia.
26. Patients with concomitant severe COPD or emphysema.
27. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
28. Female participants without adequate method of contraception
29. Inability to comply/assist with study and follow-up procedures.

4.3 Elimination criteria

1. Progression of NYHA functional class since the initiation of the study.
2. BNP or troponin I elevation
3. New onset of pulmonary infection due to opportunistic virulent antigens (N. Jirovecci, A. Baumanni, MRSA, VRSA).
4. Any serious adverse event (SAE) indicative of fatal or nonfatal hepatitis, liver failure or its complications.
5. ALT or AST >3x normal values with a total bilirubin ≥ 2x normal value.
6. WBC count < 3000/mm3
7. Anaphylactic or life-threatening hypersensitivity reactions