Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism

This study has been terminated.
(Replaced by another study)
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
First received: April 25, 2008
Last updated: November 6, 2012
Last verified: November 2012
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).

Condition Intervention Phase
Hurler's Syndrome
Maroteaux-Lamy Syndrome
Sly Syndrome
Alpha Mannosidosis
Krabbe Disease
Wolman's Disease
Niemann-Pick Disease Type B
Niemann-Pick Disease, Type C
Procedure: Stem Cell Transplantation
Drug: Cyclophosphamide
Drug: Campath-1H
Drug: Busulfan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation

Resource links provided by NLM:

Genetics Home Reference related topics: CHMP2B-related frontotemporal dementia Chanarin-Dorfman syndrome D-bifunctional protein deficiency GRN-related frontotemporal dementia Krabbe disease Niemann-Pick disease Schindler disease Wolman disease alpha-mannosidosis alpha-methylacyl-CoA racemase deficiency aspartylglucosaminuria cholesteryl ester storage disease frontotemporal dementia with parkinsonism-17 fucosidosis inclusion body myopathy with early-onset Paget disease and frontotemporal dementia leukoencephalopathy with vanishing white matter megalencephalic leukoencephalopathy with subcortical cysts mucopolysaccharidosis type VI mucopolysaccharidosis type VII peroxisomal acyl-CoA oxidase deficiency succinic semialdehyde dehydrogenase deficiency
MedlinePlus related topics: Leukodystrophies
U.S. FDA Resources

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

Primary Outcome Measures:
  • Number of Patients Achieving Engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Rate of successful engraftment - patients who achieved and sustained donor engraftment; donor chimerism by day 100 of at least 90% after undergoing hematopoietic stem cell transplantation.

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Day 100, 1 Year, 3 Years ] [ Designated as safety issue: No ]
    Number of patients alive at timepoints.

Enrollment: 18
Study Start Date: March 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intent-to-Treat
All patients treated with study regimen.
Procedure: Stem Cell Transplantation
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.
Other Name: Bone Marrow Transplant, cord blood transplant
Drug: Cyclophosphamide

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
Other Name: Cytoxan
Drug: Campath-1H

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

Other Name: Alemtuzamab
Drug: Busulfan

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

Other Name: Busulfex

Detailed Description:
This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this is a new protocol to take the place of several older protocols. While survival has been very good on the prior protocols over the past decade, incomplete engraftment has remained somewhat problematic. Therefore, we have modified the preparative regimen somewhat to increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that is more immune suppressive. In addition, we have modified the supportive care regimen. Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and biomarkers of inflammation and oxidative stress for the families that consent to these research studies.

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00668564

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00668564     History of Changes
Other Study ID Numbers: MT2008-02  0801M25202 
Study First Received: April 25, 2008
Results First Received: June 14, 2011
Last Updated: November 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
Inborn errors of metabolism
Recessive Leukodystrophies- GLD, Krabbe disease, MLD
Peroxisomal Disorders
Wolman syndrome
Niemann-Pick B patients
Niemann-Pick C subtype 2

Additional relevant MeSH terms:
Mannosidase Deficiency Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type B
Niemann-Pick Disease, Type C
Niemann-Pick Diseases
Pick Disease of the Brain
Wolman Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Cholesterol Ester Storage Disease
Communication Disorders
Connective Tissue Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Infant, Newborn, Diseases
Language Disorders
Lipid Metabolism Disorders
Lymphatic Diseases
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Mental Disorders
Metabolic Diseases
Nervous System Diseases
Neurocognitive Disorders
Neurodegenerative Diseases
Speech Disorders

ClinicalTrials.gov processed this record on May 26, 2016