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: January 22, 2015
Last verified: January 2015

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: Enriched Hematopoetic Stem Cell Transplantation/novel platform technology
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: Endpoint Classification: Safety/Efficacy Study
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:

Genetics Home Reference related topics: alpha-mannosidosis alpha-methylacyl-CoA racemase deficiency CASK-related intellectual disability Chanarin-Dorfman syndrome CHMP2B-related frontotemporal dementia cholesteryl ester storage disease D-bifunctional protein deficiency familial glucocorticoid deficiency frontotemporal dementia with parkinsonism-17 GRN-related frontotemporal dementia inclusion body myopathy with early-onset Paget disease and frontotemporal dementia Krabbe disease leukoencephalopathy with vanishing white matter MECP2 duplication syndrome megalencephalic leukoencephalopathy with subcortical cysts metachromatic leukodystrophy mucopolysaccharidosis type I mucopolysaccharidosis type II mucopolysaccharidosis type III Niemann-Pick disease peroxisomal acyl-CoA oxidase deficiency PPM-X syndrome Renpenning syndrome Sandhoff disease Schindler disease succinic semialdehyde dehydrogenase deficiency Tay-Sachs disease X-linked adrenoleukodystrophy Zellweger spectrum
U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Enriched Hematopoetic Stem Cell Engraftment [ Time Frame: One month to three years ] [ Designated as safety issue: No ]

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: Enriched Hematopoetic Stem Cell Transplant Biological: Enriched Hematopoetic Stem Cell Transplantation/novel platform technology
Bone marrow will be processed via a new technology which will enrich hematopoietic stem cells and graft facilitating cells. Monitoring for chimerism will be done at key time points.

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.


Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

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
Principal Investigator: Joanne K. Kurtzberg, MD Duke University
  More Information

No publications provided

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: January 22, 2015
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Niemann-Pick Diseases
Adrenal Gland Diseases
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hereditary Central Nervous System Demyelinating Diseases
Heredodegenerative Disorders, Nervous System
Lipid Metabolism Disorders
Lymphatic Diseases
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Mannosidase Deficiency Diseases
Metabolic Diseases
Nervous System Diseases
Peroxisomal Disorders
Leukodystrophy, Globoid Cell
Leukodystrophy, Metachromatic
Adrenal Insufficiency
Carbohydrate Metabolism, Inborn Errors
Histiocytosis, Non-Langerhans-Cell processed this record on March 30, 2015