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

This study is ongoing, but not recruiting participants.
Duke University
Information provided by (Responsible Party):
University of Louisville Identifier:
First received: June 10, 2011
Last updated: November 30, 2016
Last verified: November 2016
The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.

Condition Intervention Phase
Hurler Syndrome (MPS I)
Hurler-Scheie Syndrome With Early Neurologic Involvement and/or Sensitization to Enzyme Replacement Therapy (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
Biological: FCRx infusion
Phase 1
Phase 2

Access to an investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

Resource links provided by NLM:

Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • 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:
  • Enriched Hematopoetic Stem Cell Engraftment [ Time Frame: One month to three years ]

Estimated Enrollment: 30
Study Start Date: April 2011
Estimated Study Completion Date: April 2028
Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inherited Metabolic Disorder Patients
Recipients are treated with an FCRx infusion from living donors
Biological: FCRx infusion
Enriched hematopoetic stem cell infusion

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.

Ages Eligible for Study:   Child, Adult, Senior
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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01372228

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
University of Louisville
Duke University
Study Director: Suzanne T Ildstad, MD University of Louisville
  More Information

Responsible Party: University of Louisville Identifier: NCT01372228     History of Changes
Other Study ID Numbers: ICT-14070-010611
Study First Received: June 10, 2011
Last Updated: November 30, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Louisville:
hematopoietic stem cell transplant, chimerism, leukodystrophy

Additional relevant MeSH terms:
Metabolic Diseases
Pick Disease of the Brain
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Mannosidase Deficiency Diseases
Tay-Sachs Disease
Sandhoff Disease
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Lysosomal Storage Diseases
Connective Tissue Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Hereditary Central Nervous System Demyelinating Diseases
Demyelinating Diseases
Peroxisomal Disorders
Adrenal Gland Diseases
Endocrine System Diseases
Neurocognitive Disorders
Mental Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurodegenerative Diseases processed this record on May 22, 2017