Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism - Full Text View

Sponsors and Collaborators:	University of Minnesota Masonic Cancer Center, University of Minnesota
Information provided by:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT00668564

Purpose

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).

Condition	Intervention
Hurler's Syndrome Maroteaux-Lamy Syndrome Sly Syndrome Alpha Mannosidosis Fucosidosis Aspartylglucosaminuria Sphingolipidoses Krabbe Disease Wolman's Disease Niemann-Pick Disease Type B Niemann-Pick Disease, Type C	Procedure: Stem Cell Transplantation Drug: Campath, Busulfan, Cyclophosphamide

Genetics Home Reference related topics: alpha-mannosidosis aspartylglucosaminuria beta-ketothiolase deficiency cholesteryl ester storage disease Farber lipogranulomatosis fucosidosis Krabbe disease leukoencephalopathy with vanishing white matter long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency megalencephalic leukoencephalopathy with subcortical cysts mitochondrial trifunctional protein deficiency mucopolysaccharidosis type I Niemann-Pick disease primary carnitine deficiency Wolman disease

MedlinePlus related topics: Leukodystrophies

Drug Information available for: Cyclophosphamide Alemtuzumab Campath Busulfan

U.S. FDA Resources

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

Further study details as provided by University of Minnesota:

Primary Outcome Measures:

Survival [ Time Frame: at 100 days, 1 year and 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence and severity of graft-versus-host disease (GVHD) [ Time Frame: at day 100 ] [ Designated as safety issue: Yes ]
Incidence of viral and fungal infections [ Time Frame: at day 180 ] [ Designated as safety issue: Yes ]
Incidence of pulmonary complications [ Time Frame: at day 180 ] [ Designated as safety issue: Yes ]
Changes in neuropsychometric function [ Time Frame: at 1 year, 2 years and 3 years in comparison to baseline studies ] [ Designated as safety issue: No ]
Changes in the central nervous system in regards to progression using imaging studies (MRI) [ Time Frame: Through 3 years post BMT ] [ Designated as safety issue: No ]
time to CD4 recovery [ Time Frame: Through 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2015
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Intervention Details:

The purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the body's immune response to the substances that have accumulated in the body. These normal hematopoietic stem 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). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme.

Days before Transplant Drug Frequency

12 Campath-1H Once, given over 2 hours
11 Campath-1H Once, given over 2 hours
10 Campath-1H Once, given over 2 hours
9 Busulfan Four times per day
8 Busulfan Four times per day
7 Busulfan Four times per day
6 Busulfan Four times per day
5 Rest day; no chemotherapy
4 Cyclophosphamide Once, given over 2 hours
3 Cyclophosphamide Once, given over 2 hours
2 Cyclophosphamide Once, given over 2 hours
1 Cyclophosphamide Once, given over 2 hours

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Mucopolysaccharidosis 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 MLD will be eligible for treatment on this protocol. White matter disease by MRI alone is not an exclusion if the patient is asymptomatic.
Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders associated with of 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 asymptomatic.
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 ALT > 3 x normal
- Pulmonary: requirement for continuous oxygen supplementation
Pregnancy
Evidence of HIV infection or known HIV positive serology
Patients >21 years of age.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668564

Contacts

Contact: Paul Orchard, MD	612-626-1926	orcha001@umn.edu
Contact: Teresa Kvisto, RN	612-273-2800	tkvist1@fairview.org

Locations

United States, Minnesota
University of MInnesota, Fairview	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Tim Krepski, RN 612-273-2800
Contact: Teresa Kvisto, RN 612-273-2800 tkvist!@fairview.org

Sponsors and Collaborators

University of Minnesota

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Paul Orchard, MD

University of Minnesota Medical Center

More Information

Responsible Party:	University of Minnesota ( Paul Orchard, M.D. )
Study ID Numbers:	0801M25201, MT2008-02
Study First Received:	April 25, 2008
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00668564
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Minnesota:

Inborn errors of metabolism
Sphingolipidoses
Recessive Leukodystrophies- GLD, Krabbe disease, MLD
Peroxisomal Disorders

Wolman syndrome
Niemann-Pick B patients
Niemann-Pick C subtype 2

Study placed in the following topic categories:

Pick Disease of the Brain
Sphingolipidoses
Frontotemporal dementia
Demyelinating diseases
Brain Diseases
Alpha-L-iduronidase deficiency
Metabolism, Inborn Errors
Mucopolysaccharidoses
Alemtuzumab
Infant, Newborn, Diseases
Brain Diseases, Metabolic, Inborn
Niemann-Pick Disease
Delirium
Speech Disorders
Cholesterol Ester Storage Disease

Metabolic Diseases
Demyelinating Diseases
Lysosomal Storage Diseases
Aphasia
Language Disorders
Cognition Disorders
Fucosidosis
Niemann-Pick Disease, Type B
Niemann-Pick Disease, Type C
Delirium, Dementia, Amnestic, Cognitive Disorders
Aspartylglycosaminuria
Wolman Disease
Niemann-Pick Disease, Type A
Mucopolysaccharidosis type 6
Niemann-Pick disease, type C1

Additional relevant MeSH terms:

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

Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Syndrome
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Histiocytosis, Non-Langerhans-Cell
Alkylating Agents
Carbohydrate Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on January 16, 2009