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Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota Identifier:
First received: January 5, 2010
Last updated: January 21, 2016
Last verified: January 2016

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.

Condition Intervention Phase
Hurler Syndrome
Hunter Syndrome
Maroteaux-Lamy Syndrome
Sly Syndrome
Alpha Mannosidosis
Adrenoleukodystrophy (ALD)
Krabbe Disease
Metachromatic Leukodystrophy (MLD)
Peroxisomal Disorders
Drug: Campath-1H
Drug: Cyclophosphamide
Drug: Busulfan
Procedure: Allogeneic stem cell transplantation
Drug: Cyclosporine A
Drug: Mycophenolate Mofetil
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders

Resource links provided by NLM:

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients with Donor Derived Engraftment [ Time Frame: Day 100 Post Transplant ]

Secondary Outcome Measures:
  • Number of Patients with Graft-Versus-Host Disease (GVHD) by Severity [ Time Frame: Day 100 Post Transplant ]
  • Number of Patients Died Peri-Transplant [ Time Frame: By Day 100 Post Transplant ]
  • Donor Cell Chimerism Following Transplant [ Time Frame: Day 28, Day 42, Day 100, Month 6, Yearly Post Transplant ]

Enrollment: 46
Study Start Date: December 2009
Estimated Study Completion Date: June 2017
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant Patients
Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Drug: Campath-1H
Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)
Other Name: Alemtuzumab
Drug: Cyclophosphamide
Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.
Other Name: Cytoxan(R)
Drug: Busulfan
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
Other Name: Busulfex(R)
Procedure: Allogeneic stem cell transplantation
Administered > 24 hours after last dose of busulfan.
Other Name: stem cell transplant
Drug: Cyclosporine A

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).
Other Name: CsA
Drug: Mycophenolate Mofetil
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.
Other Name: MMF

Detailed Description:

Primary Objective:

  • To estimate the proportion of patients with donor derived engraftment at day 100 post transplant as defined by 80% or greater donor cells in the CD3 (T cell) fraction

Secondary Objectives:

  • To determine the incidence and severity of graft-versus-host disease (GVHD) by day 100
  • To determine the incidence of peri-transplant mortality (death by day 100)
  • To monitor donor cell chimerism at various time points following allogeneic transplantation with this transplant regimen as determined at day 28, 42, 100, 6 months and yearly for 5 years.

Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01043640

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01043640     History of Changes
Other Study ID Numbers: 2009LS088
MT2009-19 ( Other Identifier: Blood and Marrow Transplantation Program )
Study First Received: January 5, 2010
Last Updated: January 21, 2016

Keywords provided by Masonic Cancer Center, University of Minnesota:
inherited metabolic disorders

Additional relevant MeSH terms:
Metabolic Diseases
Leukodystrophy, Globoid Cell
Leukodystrophy, Metachromatic
Mucopolysaccharidosis I
Mannosidase Deficiency Diseases
Mucopolysaccharidosis II
Mucopolysaccharidosis VI
Peroxisomal Disorders
Mucopolysaccharidosis VII
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases processed this record on April 28, 2017