UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

NCT02254863 | Recruiting Phase 1 DMC

• 1 other identifier: Pro00050198
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

Keywords

Adrenoleukodystrophy; Batten Disease; Hunter Syndrome; Krabbe; Metachromatic Leukodystrophy; ALD; MLD; PMD

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Efficacy determination

  1-5 years

Study Arms (1)

Intrathecal administration of DUOC-01

EXPERIMENTAL

Administration of DUOC-01, given intrathecally, between day 26 and 28 post unrelated cord blood transplant

Biological: DUOC-01

Interventions

DUOC-01 BIOLOGICAL

Intrathecal administration of DUOC-01

Intrathecal administration of DUOC-01

Eligibility Criteria

• Age: 1 Week - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be age ≥1 week to ≤21 years.
• 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)
• 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.
• 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
• % 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.
• Patients must have an available, suitably matched, banked UCB unit for transplant.
• Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%

You may not qualify if:

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

Sponsors & Collaborators

• Joanne Kurtzberg, MD: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

RECRUITING

MeSH Terms

Conditions

Adrenoleukodystrophy; Neuronal Ceroid-Lipofuscinoses; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Niemann-Pick Disease, Type A; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; alpha-Mannosidosis

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Neurodegenerative Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Sulfatidosis; Niemann-Pick Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Gangliosidoses, GM2; Gangliosidoses; Mannosidase Deficiency Diseases

Study Officials

• Joanne Kurtzberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sydney Crane, RN

CONTACT

cordbloodtherapyinfo@dm.duke.edu

Erin Arbuckle

CONTACT

cordbloodtherapyinfo@dm.duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: October 2, 2014
• Study Start: September 1, 2014
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

US (1)