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

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, 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

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

Resource links provided by NLM:

Genetics Home Reference related topics: beta-ketothiolase deficiency Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis fucosidosis Gaucher disease juvenile Batten disease Krabbe disease L1 syndrome leukoencephalopathy with vanishing white matter megalencephalic leukoencephalopathy with subcortical cysts metachromatic leukodystrophy Niemann-Pick disease primary carnitine deficiency Sandhoff disease succinic semialdehyde dehydrogenase deficiency 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 Busulfan

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Overall outcome - Compare patients treated by bone marrow, peripheral blood, or umbilical cord blood transplantation after March of 2001 with historical controls with bone marrow transplant (BMT) for these patients over the last 5 years. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Survival [ Time Frame: at 100 days, 1 year and 3 years ] [ Designated as safety issue: No ]
Change in neuropsychometric function. [ Time Frame: at 6 months, 1 year, 2 years and 3 years ] [ Designated as safety issue: No ]
Toxicity of hematopoietic cell transplant therapy [ Time Frame: Day 100, 6 months, 1 year, 2 years, 3 years ] [ 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 ]
primary pharmacokinetic parameters investigated will be AUC and Cpmin of total and free MPA [ Time Frame: 0, 1, 2, 4, 6 and 8 Hours post-dose ] [ Designated as safety issue: No ]

Enrollment:	134
Study Start Date:	January 1995
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treated Patients: Experimental All patients treated with protocol regimen (chemotherapy and surgery).	Procedure: Stem Cell Transplant 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). Drug: Busulfan, Cyclophosphamide, ATG Subjects will receive BUSULFAN intravenously (IV)- patients < or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients > 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) 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.

Arms

Assigned Interventions

Treated Patients: Experimental

All patients treated with protocol regimen (chemotherapy and surgery).

Procedure: Stem Cell Transplant

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).

Drug: Busulfan, Cyclophosphamide, ATG

Subjects will receive BUSULFAN intravenously (IV)- patients < or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients > 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) 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 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 (Mannosidosis)).
Pregnancy
Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
Patients or parents are psychologically incapable of undergoing bone marrow transplant (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 peripheral blood stem cells (PBSCs)

Contacts and Locations

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

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota ( Orchard, Paul J., MD )
Study ID Numbers:	9412M09107, MT1995-01
Study First Received:	September 12, 2005
Last Updated:	September 16, 2009
ClinicalTrials.gov Identifier:	NCT00176904 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

Inborn errors
Storage disease
errors of metabolism
stem cell transplant

Additional relevant MeSH terms:

Pick Disease of the Brain
Sphingolipidoses
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenal Gland Diseases
Brain Diseases
Neurodegenerative Diseases
Hereditary Central Nervous System Demyelinating Diseases
Metabolism, Inborn Errors
Heredodegenerative Disorders, Nervous System
Therapeutic Uses
Adrenoleukodystrophy
Addison Disease
Infant, Newborn, Diseases
Brain Diseases, Metabolic, Inborn

Tay-Sachs Disease
Speech Disorders
Adrenal Insufficiency
Cholesterol Ester Storage Disease
Metabolic Diseases
Reticuloendotheliosis
Immune System Diseases
Demyelinating Diseases
Aphasia
Lysosomal Storage Diseases
Nervous System Diseases
Sulfatidosis
Language Disorders
Endocrine System Diseases
Fucosidosis

ClinicalTrials.gov processed this record on November 27, 2009