A Trial of a Single ProHema-CB Product Transplant in Pediatric Patients With Inherited Metabolic Disorders
Condition: Metabolic Disorders
MeSH terms: Metabolic Diseases
Intervention: ProHema-CB Transplant
Intervention description: ProHema-CB, the cellular product, represents the cell populations contained within a human UCB unit after modulation on the day of transplantation by an ex vivo incubation process with the prostaglandin derivative, 16,16-dimethyl prostaglandin E2 (also referred to as FT1050). The cell populations include hematopoietic stem and progenitor cells.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 1 Year
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to describe the safety profile of ProHema-CB as part of a single
      cord blood unit transplant after a myeloablative conditioning regimen in pediatric patients
      with inherited metabolic disorders. The safety profile will primarily be assessed by
      neutrophil engraftment.
    

Eligibility criteria:

        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).

        Exclusion Criteria:

          1. Evidence of HIV infection or HIV positive serology.

          2. Current uncontrolled bacterial, viral or fungal infection (progression of clinical
             symptoms despite therapy).

          3. Requirement for continuous respiratory supportive therapy (e.g. ventilator). Patients
             on intermittent respiratory support should be discussed with the Sponsor.

          4. Active problems related to chronic aspiration.

          5. Uncontrolled seizures.

          6. Any active malignancy or myelodysplastic syndrome or any history of malignancy.

          7. Inability to give informed consent/assent or to comply with the requirements for care
             after allogeneic stem cell transplantation.

          8. Female subjects that are breastfeeding or with a positive pregnancy (HCG) test at
             Screening.

          9. Use of an investigational drug within 30 days prior to screening for the primary IMD.