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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00668564
Recruitment Status : Terminated (Replaced by another study)
First Posted : April 29, 2008
Results First Posted : July 13, 2011
Last Update Posted : December 28, 2017
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief 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).

Condition or disease Intervention/treatment Phase
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 Procedure: Stem Cell Transplantation Drug: Cyclophosphamide Drug: Campath-1H Drug: Busulfan Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation
Study Start Date : March 2008
Actual Primary Completion Date : February 2010
Actual Study Completion Date : February 2010

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Number of Patients Achieving Engraftment [ Time Frame: Day 100 ]
    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 :
  1. Overall Survival [ Time Frame: Day 100, 1 Year, 3 Years ]
    Number of patients alive at timepoints.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00668564

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United States, Minnesota
University of Minnesota, Fairview
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
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Principal Investigator: Paul Orchard, MD University of Minnesota Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00668564    
Other Study ID Numbers: MT2008-02
0801M25202 ( Other Identifier: IRB, University of Minnesota )
First Posted: April 29, 2008    Key Record Dates
Results First Posted: July 13, 2011
Last Update Posted: December 28, 2017
Last Verified: December 2017
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:
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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
Niemann-Pick Disease, Type B
Metabolism, Inborn Errors
Mannosidase Deficiency Diseases
Mucopolysaccharidosis I
Wolman Disease
Mucopolysaccharidosis VI
Mucopolysaccharidosis VII
Pathologic Processes
Genetic Diseases, Inborn
Metabolic Diseases
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders