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| Sponsor: | Masonic Cancer Center, University of Minnesota |
|---|---|
| Information provided by: | Masonic Cancer Center, University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00383448 |
Purpose
Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). This protocol also considers other inherited metabolic diseases such as, but not limited to, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome or Sandhoff disease, I-cell disease (mucolipidosis II).
For patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate mofetil (MMF). In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.
| Condition | Intervention | Phase |
|---|---|---|
|
Adrenoleukodystrophy Metachromatic Leukodystrophy Globoid Cell Leukodystrophy Tay Sachs Disease Sandhoffs Disease Wolman Disease I-Cell Disease Sanfilippo Syndrome GM1 Gangliosidosis |
Drug: Clofarabine Procedure: Total body Irradiation Drug: Melphalan |
Phase II |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation |
| Estimated Enrollment: | 30 |
| Study Start Date: | September 2006 |
| Estimated Study Completion Date: | December 2011 |
| Estimated Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treated Patients
Patients receiving chemotherapy, transplantation and radiation therapy.
|
Drug: Clofarabine
5 days of: 40 mg/m2 intravenously over 2 hours
Other Name: Clolar
Procedure: Total body Irradiation
Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Other Name: TLI
Drug: Melphalan
140 mg/m2 intravenously over 30 minutes
Other Name: Alkeran
|
Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). However, for patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate mofetil (MMF), develop experience in kinetics of N-acetylcysteine, and evaluate biologic markers of oxidative status during transplantation. In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.
Eligibility| Ages Eligible for Study: | up to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Adrenoleukodystrophy: Patients from 0-55 years of age diagnosed with ALD as determined by very long chain fatty acid testing will be eligible for this protocol if they have evidence of cerebral or cerebellar disease based on MRI testing, AND they are determined high risk for any of the following reasons:
Metachromatic Leukodystrophy: Patients from 0-55 years of age diagnosed with MLD as determined by determinations of arylsulfatase A testing will be eligible for this protocol IF they are determined high risk for any of the following reasons:
Globoid Cell Leukodystrophy: Patients from 0-55 years of age diagnosed with GLD as determined by determinations of galactocerebrosidase testing will be eligible for this protocol IF they are determined high risk for any of the following reasons:
Patients with GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Wolman disease or Sandhoff disease or other inherited metabolic diseases including but not limited to I-cell disease (mucolipidosis II) who are determined to be sufficiently advanced or high risk based on the following reasons:
Exclusion criteria:
Major organ dysfunction. Evidence of major organ impairment, including:
Advanced Disease Exclusion: Following evaluation, if a consensus of the members of the Inherited Metabolic and Storage Disease Program is that a patient is too advanced to benefit in a measurable and meaningful way from transplant, this will be communicated to the family, and transplant will not be offered. Measures to assist in those determinations may include: neurologic/neurocognitive functions such as activities of daily living, motor function, vision, hearing, interaction with environment, toileting, swallowing, or other standardized measures
Contacts and Locations| Contact: Paul Orchard, M.D. | 612-626-2961 | orcha001@umn.edu |
| United States, Minnesota | |
| Masonic Cancer Center, University of Minnesota | Recruiting |
| Minneapolis, Minnesota, United States, 55455 | |
| Contact: Paul Orchard, MD 612-626-2961 orcha001@umn.edu | |
| Sub-Investigator: Kendra Bjoraker, Ph.D. | |
| Sub-Investigator: Lawrence Charnas, MD | |
| Sub-Investigator: Katherine Dusenbery, MD | |
| Sub-Investigator: Margaret MacMillan, MD | |
| Sub-Investigator: Elsa Shapiro, MD | |
| Sub-Investigator: Marcie Tomblyn, MD | |
| Sub-Investigator: Jakub Tolar, MD, Ph.D. | |
| Sub-Investigator: John Wagner, MD | |
| Sub-Investigator: Brenda Weigel, MD | |
| Principal Investigator: | Paul Orchard, MD | Masonic Cancer Center, University of Minnesota |
More Information
| Responsible Party: | Paul Orchard, M.D., Masonic Cancer Center, University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00383448 History of Changes |
| Other Study ID Numbers: | MT2006-14, 0606M87246 |
| Study First Received: | September 29, 2006 |
| Last Updated: | October 3, 2011 |
| Health Authority: | United States: Institutional Review Board |
|
Stem cell transplantation Inborn errors of metabolism Adrenoleukodystrophy (ALD) Metachromatic leukodystrophy (MLD) Globoid cell leukodystrophy (GLD or Krabbe) Tay Sachs |
Sandhoff Sanfilippo syndrome Mucopolysaccharidosis III (MPS-III) GM1 gangliosidosis I-cell mucolipidosis |
|
Gangliosidoses Mucolipidoses Leukodystrophy, Globoid Cell Leukodystrophy, Metachromatic Mucopolysaccharidosis III Sandhoff Disease Tay-Sachs Disease Wolman Disease Cholesterol Ester Storage Disease Gangliosidosis, GM1 Adrenoleukodystrophy Peroxisomal Disorders Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn |
Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases Carbohydrate Metabolism, Inborn Errors |