Stem Cell Transplant for Inborn Errors of Metabolism

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.

Condition	Intervention	Phase
Adrenoleukodystrophy Metachromatic Leukodystrophy Globoid Cell Leukodystrophy Gaucher¡¯s Disease Fucosidosis Wolman Disease Niemann-Pick Disease Batten Disease GM1 Gangliosidosis Tay Sachs Disease Sandhoff Disease	Procedure: Stem Cell Transplant  Drug: Busulfan, Cyclophosphamide, ATG	Phase II Phase III

Further study details as provided by University of Minnesota:

Primary Outcomes: We will evaluate whether patients treated by bone marrow, peripheral blood, or umbilical cord blood transplantation after March of 2001 have equivalent or better outcome than historical controls with BMT for these patients over the last 5 years.
Secondary Outcomes: estimate survival at 100 days, 1 year and 3 years.; estimate change in neuropsychometric function at 6 months, 1 year, 2 years and 3 years.; estimate the toxicity of hematopoietic cell transplant therapy:; estimate the rate of hematological donor cell engraftment.; estimate the incidence of graft-versus-host disease (GVHD).
Expected Total Enrollment:  75

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 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.

Genders Eligible for Study:  Both

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 HLA-identical or haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor. One or two UCB units may be used.
• Patients with adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, Gaucher¡¯s Disease, Fucosidosis, Wolman disease, and Niemann-Pick disease and Batten disease (CLN3) who have a HLA-identical or HLA-1 antigen mismatched unrelated marrow, or umbilical cord blood donor. One or two UCB units may be used.
• Patients with adrenoleukodystrophy must have MRI findings, neurological and neuropsychometric function consistent with the diagnosis, and for boys with parietal-occipital dysmyelination a performance IQ ¡İ80. In cases, when the performance IQ is not ¡İ80, 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 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, MPS VI, or Mannosidosis disease are no longer eligible for this protocol, but can be transplanted under protocol MT 9907.
• Pregnancy
• Evidence of HIV infection or known HIV positive serology
• Patients or parents are psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance.
• Patients ¡İ 50 kg may be at risk for having cell doses below the goal of ¡İ 10 x 106 CD34 cells/kg and therefore will not be eligible to receive unrelated PBSCs

Please refer to this study by ClinicalTrials.gov identifier  NCT00176904

Paul Orchard, M.D.      612-626-2961    orcha001@umn.edu

Minnesota
      University of Minnesota Medical Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  9412M09107; MT1995-01
Last Updated:  July 14, 2006
Record first received:  September 12, 2005
ClinicalTrials.gov Identifier:  NCT00176904
Health Authority: United States: Institutional Review Board

 

Stem Cells and Stem Cell Transplantation (National Library of Medicine)

Stem Cells: Scientific Progress and Future Research Directions  (National Institutes of Health)

Stem Cell Transplant  (Mayo Foundation for Medical Education and Research)

Stem Cell Information  (National Institutes of Health)

Understanding Cancer Series: Blood Stem Cell Transplants  (National Cancer Institute)

Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers  (National Cancer Institute)

Adult Mouse Muscle Stem Cells Are Capable of Long-Term Self-Renewal  (National Institute of Arthritis and Musculoskeletal and Skin Diseases)

National Marrow Donor Program: Glossary  (National Marrow Donor Program)

Human Periodontal Ligament Stem Cells Isolated for the First Time  (National Institute of Dental and Craniofacial Research)

How to Be a Bone Marrow or Blood Stem Cell Donor  (Mayo Foundation for Medical Education and Research)