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Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01372228
Recruitment Status : Active, not recruiting
First Posted : June 13, 2011
Last Update Posted : September 12, 2019
Duke University
Information provided by (Responsible Party):
University of Louisville

Brief Summary:
The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.

Condition or disease Intervention/treatment Phase
Hurler Syndrome (MPS I) Hurler-Scheie Syndrome Hunter Syndrome (MPS II) Sanfilippo Syndrome (MPS III) Krabbe Disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Adrenoleukodystrophy (ALD and AMN) Sandhoff Disease Tay Sachs Disease Pelizaeus Merzbacher (PMD) Niemann-Pick Disease Alpha-mannosidosis Biological: hematopoietic stem cell infusion Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Detailed Description:
The objective for the study is to establish chimerism following reduced intensity conditioning with no grade III/IV GVHD. The primary endpoint we will follow is production of the missing enzyme at ≥ 10% of the normal level at day 180 post-transplant in > 90% of patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
Study Start Date : April 2011
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : April 2028

Arm Intervention/treatment
Experimental: Inherited Metabolic Disorder Patients
Recipients are treated with hematopoietic stem cell infusion from living donors
Biological: hematopoietic stem cell infusion
Enriched hematopoetic stem cell infusion

Primary Outcome Measures :
  1. Production of missing enzyme at levels greater than or equal to 10% of normal [ Time Frame: Day 180 post transplant to three years ]

Secondary Outcome Measures :
  1. Enriched Hematopoetic Stem Cell Engraftment [ Time Frame: One month to three years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.

    Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:

    • Hurler Syndrome (MPS I)
    • Hurler-Scheie Syndrome with early neurologic involvement and/or sensitization to ERT
    • Hunter Syndrome (MPS II)
    • Sanfilippo Syndrome (MPS III)
    • Krabbe Disease (Globoid Leukodystrophy)
    • Metachromatic Leukodystrophy (MLD)
    • Adrenoleukodystrophy (ALD and AMN)
    • Sandhoff Disease
    • Tay Sachs Disease
    • Pelizaeus Merzbacher (PMD)
    • Niemann-Pick Disease
    • Alpha-mannosidosis
  2. Patients must have adequate function of other organ systems as measured by:

    • Creatinine less than or equal to 2.0 mg/dl and creatinine clearance ≥60 cc/min/1.73m2. Newborns must have a creatinine clearance ≥ 25 cc/min. For babies less than or equal to 3 months of age, the raw value on glomerular filtration rate (GFR) must be ≥ 1 cc/kg/min.
    • Hepatic transaminases (ALT/AST) 2.5 x normal, bilirubin <2.0mg/dl
    • Normal cardiac function by echocardiogram or radionuclide scan (ejection fraction or shortening fraction >80% of normal value for age)
    • Pulmonary function tests (PFTs) demonstrating forced expiratory volume at one second (FEV1) of ≥50% of predicted for age. If child is too young or unable to perform PFTs, crying vital capacity result of >50% of normal value for age or resting pulse oximeter >92% on room air or clearance by pulmonologist will be required.
  3. Patient must have a related donor (identical or mismatched for 1, 2 or 3 Human Leukocyte Antigen (HLA)-A, -B or -DR loci).
  4. Patient, and parent, or legal guardian must have given written informed consent according to FDA guidelines.
  5. Patients must have a minimum life expectancy of at least 6 months.
  6. Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).
  7. There is no upper or lower age limit for this study.

Exclusion Criteria

  1. Patients with uncontrolled seizures, apnea, evidence of recurrent or uncontrolled aspiration, or need for chronic mechanical ventilation.
  2. Patients with allogeneic stem cell transplant with cytoreductive therapy in the past 6 months.
  3. Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by radiation therapist)
  4. Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate reduced intensity transplantation.
  5. Subjects with a positive human immunodeficiency virus (HIV) antibody test result
  6. Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotropin (HCG) test
  7. Subjects whose only donor is pregnant at the time of intended transplant
  8. Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site
  9. Jehovah's witnesses being unwilling to be transfused
  10. Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
  11. Lack of related donors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01372228

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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
University of Louisville
Duke University
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OverallOfficial: Suzanne T Ildstad, MD University of Louisville
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Responsible Party: University of Louisville Identifier: NCT01372228    
Other Study ID Numbers: ICT-14070-010611
First Posted: June 13, 2011    Key Record Dates
Last Update Posted: September 12, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Louisville:
hematopoietic stem cell Tx, chimerism, leukodystrophy
Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Pick Disease of the Brain
Leukodystrophy, Metachromatic
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Tay-Sachs Disease
Leukodystrophy, Globoid Cell
Sandhoff Disease
Mannosidase Deficiency Diseases
Mucopolysaccharidosis I
Mucopolysaccharidosis III
Metabolic Diseases
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lysosomal Storage Diseases