Stem Cell Transplant for Inborn Errors of Metabolism

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Brief Title

Stem Cell Transplant for Inborn Errors of Metabolism

Official Title

Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation

Brief Summary

      The purpose of this study is to determine the safety and engraftment of donor hematopoietic
      cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming)
      cell transplant for an inherited metabolic storage disease.

Detailed Description

      Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman
      line four times daily for 4 days, Cyclophosphamide intravenously via the Hickman line once a
      day for 4 days, and Anti-Thymocyte Globulin (ATG) intravenously (IV) via the Hickman line
      twice daily for three days before the transplant. These three drugs are being given to
      subjects to help the new marrow "take" and grow.

      On the day of transplantation, the donor's hematopoietic cells will be transfused via central
      venous catheter.

      After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and
      either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone
      or MMF are given to help prevent the complication of graft-versus-host disease and to
      decrease the chance that the new donor cells will be rejected.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Overall Survival

Secondary Outcome

 Overall Donor Engraftment




Stem Cell Transplant

Study Arms / Comparison Groups

 Treated Patients
Description:  All patients treated with protocol regimen (chemotherapy and surgery).


* 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

January 1995

Completion Date

June 2010

Primary Completion Date

June 2010

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell
             leukodystrophy, Gaucher's disease, Fucosidosis, Wolman disease, Niemann-Pick disease
             and Batten disease (CLN3) who have a human leukocyte antigen (HLA)-identical or
             haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor.
             One or two umbilical cord blood (UCB) units may be used.

          -  Patients with GM1 gangliosidosis, Tay Sachs disease or Sandhoff disease who have a
             HLA-identical or 1 antigen mismatched related or unrelated donor, or suitably matched
             umbilical cord blood unit(s). One or two UCB units may be used.

          -  Patients with adrenoleukodystrophy must have magnetic resonance imaging (MRI)
             findings, neurological and neuropsychometric function consistent with the diagnosis,
             and for boys with parietal-occipital dysmyelination a performance intelligence
             quotient (IQ) ≥80. In cases, when the performance IQ is not ≥80, the protocol
             committee may recommend transplant if the patient's clinical condition and
             neuropsychometric status are deemed to be acceptable based upon consideration of such
             factors as age at onset of cerebral disease, magnitude of change in performance IQ and
             neurologic deficits.

          -  Patients with arylsulfatase A deficiency (Metachromatic Leukodystrophy) must have
             either the presymptomatic late infantile, juvenile or adult form of the disease and
             must have acceptable neurological and neuropsychometric function.

          -  Patients with galactocerebrosidase deficiency (Globoid Cell Leukodystrophy) must have
             acceptable neurological and neuropsychometric function.

          -  Patients with acid lipase deficiency (Wolman disease) must have a liver biopsy that
             documents no evidence of hepatic cirrhosis, and acceptable neurological and
             neuropsychometric function.

          -  Patients with fucosidase deficiency (Fucosidosis) must have acceptable neurological
             and neuropsychometric function.

          -  Patients with glucocerebrosidase deficiency (Gaucher's Disease) must have acceptable
             neurologic and neuropsychometric function.

          -  Patients with Batten's disease (CLN3) must have acceptable Neurological and
             neuropsychometric function.

          -  Absence of major organ dysfunction. Organ evaluation results as follows:

          -  Cardiac: ejection fraction >30%

          -  Renal: serum creatinine <2x normal or creatinine clearance 60 mL/min.

          -  Hepatic: total bilirubin <2x normal and Aspartate aminotransferase (AST) <2x normal

          -  Signed consent.

        Exclusion Criteria:

          -  Patients with symptomatic late infantile form of metachromatic leukodystrophy.

          -  Patients with symptomatic infantile globoid leukodystrophy.

          -  Note: Patients with Hurler syndrome, mucopolysaccharidosis (MPS) VI, or Mannosidosis
             disease are no longer eligible for this protocol, but can be transplanted under
             protocol MT 9907 (NCT00176917 - Hematopoietic Cell Transplantation for Hurler
             Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency

          -  Pregnancy

          -  Evidence of human immunodeficiency virus (HIV) infection or known HIV positive

          -  Patients or parents are psychologically incapable of undergoing bone marrow transplant
             (BMT) with associated strict isolation or documented history of medical

          -  Patients ≥ 50 kg may be at risk for having cell doses below the goal of ≥ 10 x 10^6
             CD34 cells/kg and therefore will not be eligible to receive unrelated peripheral blood
             stem cells (PBSCs)




N/A - N/A

Accepts Healthy Volunteers



Paul Orchard, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Masonic Cancer Center, University of Minnesota

Study Sponsor

Paul Orchard, MD, Principal Investigator, Masonic Cancer Center, University of Minnesota

Verification Date

December 2017