Stem Cell Transplant for Inborn Errors of Metabolism - Full Text View

Sponsors and Collaborators:	Orchard, Paul J., MD Masonic Cancer Center, University of Minnesota
Information provided by:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176904

Purpose

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

Genetics Home Reference related topics: beta-ketothiolase deficiency cholesteryl ester storage disease familial encephalopathy with neuroserpin inclusion bodies Farber lipogranulomatosis fucosidosis Gaucher disease GM2-gangliosidosis, AB variant Krabbe disease L1 syndrome leukoencephalopathy with vanishing white matter long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency megalencephalic leukoencephalopathy with subcortical cysts metachromatic leukodystrophy mitochondrial trifunctional protein deficiency Niemann-Pick disease primary carnitine deficiency Sandhoff disease Tay-Sachs disease Wolman disease X-linked adrenoleukodystrophy

MedlinePlus related topics: Addison's Disease Bone Marrow Transplantation Gaucher's Disease Leukodystrophies Tay-Sachs Disease

Drug Information available for: Cyclophosphamide Methylprednisolone Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation

Further study details as provided by University of Minnesota:

Primary Outcome Measures:

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. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

estimate survival. [ Time Frame: at 100 days, 1 year and 3 years ] [ Designated as safety issue: No ]
estimate change in neuropsychometric function. [ Time Frame: at 6 months, 1 year, 2 years and 3 years ] [ Designated as safety issue: No ]
estimate the toxicity of hematopoietic cell transplant therapy: [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]
estimate the rate of hematological donor cell engraftment. [ Time Frame: through 6 months, 1 year, 2 years and 3 years ] [ Designated as safety issue: No ]
estimate the incidence of graft-versus-host disease (GVHD). [ Time Frame: Through 3 years post BMT ] [ Designated as safety issue: No ]

Enrollment:	135
Study Start Date:	January 1995
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Intervention Details:

The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains an enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic 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).

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 help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

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 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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 ≥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 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 ≥ 50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD34 cells/kg and therefore will not be eligible to receive unrelated PBSCs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176904

Locations

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

Sponsors and Collaborators

Orchard, Paul J., MD

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

University of Minnesota Medical Center

More Information

Responsible Party:	University of Minnesota ( Orchard, Paul J., MD )
Study ID Numbers:	9412M09107, MT1995-01
Study First Received:	September 12, 2005
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00176904
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Minnesota:

Inborn errors
Storage disease
errors of metabolism
stem cell transplant

Study placed in the following topic categories:

Pick Disease of the Brain
Sphingolipidoses
Frontotemporal dementia
Methylprednisolone
Adrenal Gland Diseases
Demyelinating diseases
Tay-Sachs disease
Hypoadrenalism
Brain Diseases
Neurodegenerative Diseases
Metabolism, Inborn Errors
Heredodegenerative Disorders, Nervous System
Adrenoleukodystrophy
Addison Disease
Infant, Newborn, Diseases

Spielmeyer-Vogt disease
Metachromatic leukodystrophy
Brain Diseases, Metabolic, Inborn
Tay-Sachs Disease
Sandhoff disease
Niemann-Pick Disease
Delirium
Adrenal Insufficiency
Speech Disorders
Cholesterol Ester Storage Disease
Metabolic Diseases
Demyelinating Diseases
Lysosomal Storage Diseases
Aphasia
Language Disorders

Additional relevant MeSH terms:

Reticuloendotheliosis
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Lysosomal Storage Diseases, Nervous System
Nervous System Diseases
Physiological Effects of Drugs
Sulfatidosis
Hereditary Central Nervous System Demyelinating Diseases

Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Histiocytosis, Non-Langerhans-Cell
Mental Retardation, X-Linked
Alkylating Agents
Carbohydrate Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on January 16, 2009