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

Brief Title

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

Official Title

Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation

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).

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.

Study Phase

Phase 2

Study Type


Primary Outcome

Number of Patients Achieving Engraftment

Secondary Outcome

 Overall Survival


Hurler's Syndrome


Stem Cell Transplantation

Study Arms / Comparison Groups

Description:  All patients treated with study regimen.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

March 2008

Completion Date

February 2010

Primary Completion Date

February 2010

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

          -  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

          -  Patients >21 years of age.




N/A - 21 Years

Accepts Healthy Volunteers



Paul Orchard, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Masonic Cancer Center, University of Minnesota

Study Sponsor

Paul Orchard, MD, Principal Investigator, University of Minnesota Medical Center

Verification Date

December 2017