Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
Condition: Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders
MeSH terms: Adrenoleukodystrophy; Mucopolysaccharidosis II; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; Sphingolipidoses; Fucosidosis; Mucopolysaccharidoses; Mannosidase Deficiency Diseases; alpha-Mannosidosis; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Peroxisomal Disorders; Mucopolysaccharidosis VII; Aspartylglucosaminuria; Metabolic Diseases; Syndrome
Intervention: Campath-1H; Cyclophosphamide; Busulfan; Allogeneic stem cell transplantation; Cyclosporine A; Mycophenolate Mofetil
Intervention description: Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV); Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.; Administered every 6 hours: If < or = 12 kg then 1.1 mg/kg/dose intravenous (IV). If > 12 kg then 0.8 mg/kg/dose IV; Administered > 24 hours after last dose of busulfan.; 2.5 mg/kg/dose intravenous (IV_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight:
If body weight is ≤ 40 kg dosing will be 3 times daily
If body weight is > 40 kg dosing will be 2 times daily An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2 times the current IV dose (maximum 12.5 mg/kg/day as initial oral dose).; 15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: The same dosage is used orally or intravenously. Stop MMF at day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Busulfan; Alemtuzumab; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: inherited metabolic disorders

Summary:

      Rationale: Chemotherapy administration before a donor stem cell transplant is necessary to
      stop the patient's immune system from rejecting the donor's stem cells. When healthy stem
      cells from a donor are infused into the patient, the donor white blood cells can provide the
      missing enzyme that causes the metabolic disease. Sometimes the transplanted cells from a
      donor can make an immune response against the body's normal cells. Giving a monoclonal
      antibody, alemtuzumab, before transplant and cyclosporine and mycophenolate mofetil before
      and after transplant may stop this from happening. This may be an effective treatment for
      inherited metabolic disorders.

      Purpose: The design of this study is to achieve donor cell engraftment in patients with
      standard-risk inherited metabolic diseases with limited peri-transplant morbidity and
      mortality. This will be achieved through the administration of the chemotherapy regimen
      described. The intention is to follow transplanted patient for years after transplant
      monitoring them for complications of their disease and assisting families with a multifaceted
      interdisciplinary approach.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have diagnosis of one of the following: mucopolysaccharidosis disorder,
             glycoprotein metabolic disorder, sphingolipidoses or inherited leukodystrophy,
             peroxisomal disorder or other inherited diseases of metabolism

          -  Must have an acceptable graft source as defined by University of Minnesota criteria

          -  Adequate organ function

        Exclusion Criteria:

          -  Pregnant - menstruating females must have a negative serum pregnancy test within 14
             days of treatment start

          -  Evidence of human immunodeficiency virus (HIV) infection or known HIV positive
             serology