Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism
Condition: Hurler's Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Sphingolipidoses; Krabbe Disease; Wolman's Disease; Niemann-Pick Disease Type B; Niemann-Pick Disease, Type C
MeSH terms: Pick Disease of the Brain; Aphasia, Primary Progressive; Frontotemporal Dementia; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Leukodystrophy, Globoid Cell; Sphingolipidoses; Fucosidosis; Niemann-Pick Disease, Type B; Metabolism, Inborn Errors; Mannosidase Deficiency Diseases; alpha-Mannosidosis; Mucopolysaccharidosis I; Wolman Disease; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; Aspartylglucosaminuria; Syndrome
Intervention: Stem Cell Transplantation; Cyclophosphamide; Campath-1H; Busulfan
Intervention description: The purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the body's immune response to the substances that have accumulated in the body. These normal hematopoietic stem cells can come from bone marrow, peripheral blood (i.e., the blood circulating in our body's blood vessels) or umbilical cord blood (i.e., blood taken from the umbilical cord after a baby is born and umbilical cord is cut). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme.; Days before Transplant Drug Frequency
4 Cyclophosphamide Once, given over 2 hours
3 Cyclophosphamide Once, given over 2 hours
2 Cyclophosphamide Once, given over 2 hours
1 Cyclophosphamide Once, given over 2 hours; Days before Transplant Drug Frequency
12 Campath-1H Once, given over 2 hours
11 Campath-1H Once, given over 2 hours
10 Campath-1H Once, given over 2 hours; Days before Transplant Drug Frequency
9 Busulfan Four times per day
8 Busulfan Four times per day
7 Busulfan Four times per day
6 Busulfan Four times per day
Intervention MeSH terms: Cyclophosphamide; Busulfan; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Inborn errors of metabolism; Sphingolipidoses; Recessive Leukodystrophies- GLD, Krabbe disease, MLD; Peroxisomal Disorders; Wolman syndrome; Niemann-Pick B patients; Niemann-Pick C subtype 2

Summary:

      The primary objective of this clinical trial is to evaluate the ability to achieve and
      sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of
      metabolism undergoing hematopoietic stem cell transplantation (HCT).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Mucopolysaccharidosis (MPS) Disorders:

               -  MPS IH (Hurler syndrome)

               -  MPS-VI (Maroteaux-Lamy syndrome)

               -  MPS VII (Sly syndrome).

          -  Glycoprotein metabolic disorders:

               -  Alpha mannosidosis

               -  Fucosidosis

               -  Aspartylglucosaminuria

          -  Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with globoid
             cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic
             leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter
             disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient
             is asymptomatic.

          -  Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders
             associated with of very long chain fatty acids (VLCFA) elevation, identified by family
             history or laboratory testing (including neonatal screening), are eligible for this
             protocol. White matter disease by MRI alone is not an exclusion if the patient is
             asymptomatic.

          -  Other Inherited Diseases of Metabolism:

               -  Wolman syndrome (acid lipase deficiency)

               -  Niemann-Pick B patients (sphingomyelin deficiency)

               -  Niemann-Pick C subtype 2

          -  Donor Availability: Patients considered for transplantation must have a sufficient
             graft as based on current criteria of the University of Minnesota Blood and Marrow
             Transplantation Program: Priority will be as follows, although in circumstances in
             which timing is of the essence, cord blood grafts may be chosen over an unrelated
             graft, despite the priority listed above.

          -  Multidisciplinary Evaluation: Patients will be eligible for transplantation only after
             they are seen and evaluated by members of the Inherited Metabolic and Storage Disease
             Program (IMSD) team, and the team has offered transplantation to the patient/family.

        Exclusion Criteria:

          -  Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be
             considered for other treatment protocols.

          -  Major organ dysfunction. Evidence of major organ impairment, including:

               -  Cardiac: left ventricular ejection fraction <40%

               -  Renal: serum creatinine >2.5 x normal for age

               -  Hepatic: total bilirubin >3 x normal, or Alanine transaminase (ALT) > 3 x normal

               -  Pulmonary: requirement for continuous oxygen supplementation

          -  Pregnancy

          -  Evidence of human immunodeficiency virus (HIV) infection or known HIV positive
             serology

          -  Patients >21 years of age.