UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells (DUOC-01)

Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells

The primary objective of the study is to determine the safety and feasibility of intrathecal administration of DUOC-01 in patients who are undergoing standard treatment with umbilical cord blood transplant (UCBT) for inborn errors of metabolism and who have evidence of early demyelinating disease in the central nervous system (CNS). The secondary objective of the study is to describe the efficacy of UCBT with intrathecal administration of DUOC-01 in these patients.

Study Overview

• Status: Recruiting
• Conditions: Mucopolysaccharidosis II; Brain Diseases, Metabolic, Inborn; Adrenoleukodystrophy; Batten Disease; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; Alpha-Mannosidosis; Tay-Sachs Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Neimann Pick Disease; Sanfilippo Mucopolysaccharidoses
• Intervention / Treatment: Biological: DUOC-01

Detailed Description

The inherited metabolic disorders (IMD) are a group of genetic diseases, most of which involve a single gene mutation, resulting in an enzyme defect. In the majority of cases, the enzyme defect leads to the buildup of substances that are toxic and/or interfere with normal cellular function. Often times, patients may appear normal at birth but during infancy begin to exhibit disease symptoms, frequently including progressive neurological deterioration due to absent or abnormal brain myelination. The ultimate result is death in later infancy or childhood.

Currently, the only effective therapy to slow or halt this neurologic decline is allogeneic hematopoietic stem cell transplantation (HSCT). The engraftment of donor cells in a patient with an IMD provides a constant source of enzyme replacement, thereby slowing or halting the progression of disease. However, one barrier to the success of HSCT is the slower engraftment of donor cells in the central nervous system (CNS), which is associated with ongoing disease progression over 2-4 months before stabilization.

This study will evaluate the safety of an additional cell therapy for patients who are receiving HSCT using umbilical cord blood (UCB) cells from an allogeneic (non-self) donor for treatment of an IMD that is known to benefit from HSCT. The additional cell therapy, UCB-derived oligodendrocyte-like cells (DUOC-01), will serve as a supplementary therapy to a standard UCB transplant. DUOC-01 is administered intrathecally (injected into the spinal fluid) after transplant. The goal of this therapy is to accelerate delivery of donor cells to the CNS, thereby bridging the gap between the time from UCB transplant to engraftment of the UCB cells in the CNS, with the goal of preventing disease progression.

This study is only performed at Duke University Medical Center and only patients who are medically eligible for a UCB transplant will be enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sydney Crane, RN; Email: cordbloodtherapyinfo@dm.duke.edu
• Study Contact Backup: Name: Erin Arbuckle; Email: cordbloodtherapyinfo@dm.duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
      • Contact: Sydney Crane, RN; Email: cordbloodtherapyinfo@dm.duke.edu
      • Principal Investigator: Joanne Kurtzberg, MD
      • Sub-Investigator: Jessica Sun, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must be age ≥1 week to ≤21 years.

2. Patients must have one of the following inherited metabolic diseases detected by enzyme or mutation analysis, and confirmed by repeat testing on a separately obtained sample:

   Adrenoleukodystrophy (ALD) Batten Disease Hunter Syndrome (MPS II) Krabbe disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Niemann Pick disease type A or B Pelizaeus-Merzbacher disease (PMD) Sandhoff disease Tay Sachs disease. Alpha Mannosidosis Sanfilippo (MPS III)

3. Patients must have neurologic evidence of their disease, either clinically or via neuroimaging or neurophysiological testing. Examples of evidence of neurologic involvement include, but are not limited to the following:

   • Abnormal EEG, Brainstem Auditory Evoked Response (BAER), and/or Visual Evoked Potentials (VEP).
   • Abnormal brain MRI, ie. increased Loes score (measure of white matter damage, demyelination, and brain atrophy) and/or abnormal corticospinal tracts as assessed by MRI with diffusion tensor imaging (DTI).
   • Three or more of the early clinical markers: problems sleeping, increased activity, behavior difficulties, seizure-like activity, chewing behavior, inappropriate bladder training, inappropriate bowel training.

4. Patients must have adequate organ function as measured by:

   • Renal: Serum creatinine ≤ 2.0 mg/dl
   • Hepatic: Hepatic transaminases (ALT/AST) ≤ 5 x normal, bilirubin ≤ 2.0 mg/dl (except in patients with Gilbert's disease or newborns with physiological or breast milk associated jaundice).

   • Cardiac: Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction

     • 80% of normal value for age). Patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide.
   • Pulmonary: Pulmonary function tests demonstrating FVC, FEV1, and DLCO ≥ 60% of predicted in patients who can complete the testing. If patient cannot perform PFT's, an O2 sat must be >90% on room air.
5. Patients must have an available, suitably matched, banked UCB unit for transplant.
6. Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%
7. Patients must have a life expectancy of ≥ 6 months.

Exclusion Criteria:

1. Prior organ, tissue, or stem cell transplant within 3 years of study entry.
2. Prior participation in any gene or regenerative cell therapy study.
3. Inability to have an MRI scan or lumbar puncture.
4. Intractable seizures.
5. Chronic aspiration.
6. Bleeding disorder.
7. Evidence of HIV infection or HIV positive serology.
8. Uncontrolled bacterial, viral, or fungal infection at the time of pre-UCBT cytoreduction.
9. Inability to obtain patient's, parent's or legal guardian's consent.
10. Requirement of ventilatory support.
11. Pregnant or breastfeeding.
12. Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive medications, or cytotoxic chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrathecal administration of DUOC-01; Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant	Biological: DUOC-01; Intrathecal administration of DUOC-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate for Infusional Toxicity	Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness	24 hours after infusion
Evaluate for Neuro Toxicity	Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration	1 month after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy determination	Perform standard of care follow-up evaluations to include brain magnetic resonance imaging (MRI) with diffuse tensor imaging (DTI), Electroencephalography (EEG), nerve conduction, brainstem auditory evoked response (BAER), visual evoked potential (VEP) and neurocognitive testing. Bench mark results against historical controls previously transplanted by our institution for the past 20 years.	1-5 years

Collaborators and Investigators

• Sponsor: Joanne Kurtzberg, MD
• Collaborators: The Marcus Foundation
• Investigators: Principal Investigator: Joanne Kurtzberg, MD, Duke University

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimated): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): September 3, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Hunter Syndrome; Adrenoleukodystrophy; PMD; MLD; ALD; Batten Disease; Krabbe; Metachromatic Leukodystrophy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Neurobehavioral Manifestations; Demyelinating Diseases; Neurodegenerative Diseases; Lymphatic Diseases; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Adrenal Gland Diseases; Intellectual Disability; Genetic Diseases, X-Linked; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Brain Diseases, Metabolic; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Sphingolipidoses; Lipidoses; Mucopolysaccharidoses; Adrenal Insufficiency; Sulfatidosis; Peroxisomal Disorders; Gangliosidoses, GM2; Gangliosidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; X-Linked Intellectual Disability; Niemann-Pick Diseases; Mannosidase Deficiency Diseases; Mucopolysaccharidosis II; Niemann-Pick Disease, Type A; Neuronal Ceroid-Lipofuscinoses; Adrenoleukodystrophy; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; alpha-Mannosidosis; Pelizaeus-Merzbacher Disease; Tay-Sachs Disease; Sandhoff Disease; Brain Diseases, Metabolic, Inborn
• Other Study ID Numbers: Pro00050198

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: No