A Trial of a Single ProHema-CB Product Transplant in Pediatric Patients With Inherited Metabolic Disorders

Inclusion Criteria

• •1. Patients must have a confirmed diagnosis of an inherited metabolic disorder (IMD) and be amenable to treatment by hematopoietic cell transplantation:
• •* Mucopolysaccharidoses: Hurler Syndrome (MPS IH), MPS I-HS (Hurler-Scheie Syndrome), Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), or MPS VI (Maroteaux-Lamy syndrome) with early neurologic involvement and/or sensitization to enzyme replacement therapy (ERT); or
• •* Leukodystrophies: Krabbe disease (Globoid Leukodystrophy), Metachromatic Leukodystrophy (MLD), Adrenoleukodystrophy (ALD and AMN); or
• •* Other IMD with lysosomal storage disorder including glycoproteinoses (Alpha-Mannosidosis, Mucolipidosis II or I-Cell disease), sphingo- and other lipidoses (Sandhoff disease, Tay Sachs disease, Pelizaeus Merzbacher (PMD), Niemann-Pick disease, GM1 gangliosidosis, Wolman's disease.
• •2. Male and female subjects aged 1 to 18 years, inclusive.
• •3. Lack of 4 6/6 HLA matched non-carrier related UCB or 8/8 HLA A, B, C, DRß1 matched non-carrier related or 8/8 unrelated bone marrow donor; or donor not available within appropriate timeframe, as determined by the transplant physician.
• •4. Availability of suitable primary and secondary umbilical cord blood (UCB) units.
• •5. Adequate performance status, defined as:
• •* Subjects ≥ 16 years: Karnofsky score ≥ 70%.
• •* Subjects \< 16 years: Lansky score ≥ 70%.
• •6. Cardiac: Left ventricular ejection fraction at rest must be \> 40%, or shortening fraction \> 26%.
• •7. Pulmonary:
• •* Subjects \> 10 years: DLCO (diffusion capacity) \> 50% of predicted (corrected for hemoglobin)
• •* FEV1, FVC \> 50% of predicted; Note: If unable to perform pulmonary tests, then O2 saturation \> 92% on room air.
• •8. Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \> 70mL/min/1.73m2.
• •9. Hepatic: Bilirubin ≤ 2.5 mg/dL (except in the case of Gilbert's syndrome, ongoing hemolytic anemia, or due to the primary IMD); and ALT, AST and Alkaline Phosphatase ≤ x 3 ULN (all elevations beyond the ULN must be secondary to the primary IMD and not a comorbid condition).
• •10. Signed IRB approved Informed Consent Form (ICF).