Autologous Stem Cell Transplantation of Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease

Inclusion Criteria: 1. Male patients 18-50 years of age at the time of enrollment 2. Diagnosis of Fabry disease (FD) as defined by very low or absent α-gal A activity 3. Classic FD Type I phenotype with alpha-galactosidase A (GLA) genotyping 4. Patients on enzyme replacement therapy (ERT) prior to enrollment 5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1 6. Adequate organ function within 21 days prior to Pre-Treatment Phase: 7. Willing and capable of signing and giving written informed consent in accordance with Research Ethics Board (REB) requirements 8. Willing to comply with all procedures outlined in the study protocol, cooperative with the protocol schedule, able to return for safety evaluation, or otherwise likely to complete the study 9. Willing to abstain from sexual activity or willing to use condoms during sexual intercourse from day of Melphalan administration on day -1 of Phase 3 until after 12 months follow-up post-transplant. 10. Willing to not donate sperm after receiving Melphalan. Sperm banking will be recommended to any patient who would like to father children in the future. Exclusion Criteria: 1. Males with variant Fabry Disease. 2. Female gender 3. Use of immunosuppressive agents or any anticoagulant 4. Ongoing ERT-related infusion associated reactions of moderate-to-severe intensity 5. Presence of anti-agalsidase immunoglobulin (Ig)G antibodies above a threshold (5-fold above normal;) or evidence of high titre neutralizing antibodies 6. Blood test positive for Hepatitis B virus (HBV), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-cell lymphotropic virus type 1 (HTLV-1), human T-cell lymphotropic virus type 1 (HTLV-2), or Venereal Disease Research Laboratory test (VDRL; Transmissible Disease (TD) testing will be done in Pre-Treatment Phase 2 - see section 5.1 for full panel of TD tests. Patients will only be excluded from the study if positive for the TD tests listed here in this exclusion). 7. Uncontrolled bacterial, viral, or fungal infections 8. Prior malignancies except resected basal cell carcinoma 9. Chronic Kidney Disease (CKD) stage \>2 10. History of heart failure or left ventricle ejection fraction (LVEF) \<45% or moderate to severe diastolic dysfunction by standard criteria 11. Arrhythmia: bundle branch block, heart block degree II or III, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrest, pacemaker, implantable cardiac defibrillator 12. Coronary artery disease with angina, prior myocardial infarction, percutaneous transluminal coronary angioplasty with or without stent, coronary artery bypass graft surgery, moderate to severe valvular heart disease, valve replacement surgery 13. Uncontrolled hypertension 14. Diabetes mellitus 15. Advanced liver disease, liver failure, cirrhosis 16. Immune deficiency state 17. Moderate-to-severe chronic obstructive pulmonary disease (COPD) 18. Any hematological condition with white blood cells (WBC) \<3.0 x109/L, platelet count \<100 x109/L, and/or hemoglobin \<100 g/L 19. Prior bone marrow transplant (BMT) or organ transplant 20. Any condition that would preclude use of Melphalan 21. Use of a drug with cytotoxic or immunosuppressive effect within 60 days of trial entry 22. Uncontrolled psychiatric disorder 23. Active chronic infection 24. Prior tuberculosis 25. Any other serious concurrent disease 26. Cognitive impairment that would prevent informed consent 27. Use of an investigational drug within 30 days of stem cell transplant (SCT)