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

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Brief Title

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

Official Title

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

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.

Detailed Description

      The inherited metabolic disorders (IMD) are a heterogeneous 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 accumulation of substrates 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 manifestations, 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 halt the neurologic progression of disease is
      allogeneic hematopoietic stem cell transplantation (HSCT), which serves as a source of
      permanent cellular ERT.3 However, one barrier to the success of this therapy is delayed
      engraftment of donor cells in the CNS when administered through the intravenous route, which
      is associated with ongoing disease progression over 2-4 months before stabilization. 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.

      This study will evaluate the safety of a potential new treatment for patients with certain
      IMDs known to benefit from HSCT using allogeneic UCB donor cells. The new intervention,
      intrathecal administration of UCB-derived oligodendrocyte-like cells (DUOC-01) will serve as
      an adjunctive therapy to a standard UCB transplant. The goal of this therapy is to accelerate
      delivery of donor cells to the CNS thereby bridging the gap between systemic transplant and
      engraftment of cells in the CNS and preventing disease progression. The DUOC-01 cells and
      cells used for HSCT will be derived from the same UCB donor unit.

Study Phase

Phase 1

Study Type


Primary Outcome

Evaluate for Infusional Toxicity

Secondary Outcome

 Efficacy determination





Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

September 2014

Completion Date

September 2022

Primary Completion Date

September 2022

Eligibility Criteria

        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

             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 not have a suitable fully matched, non-carrier sibling or related bone
             marrow donor.

          6. Patients must have an available, suitably matched, banked UCB unit in a
             two-compartment configuration (see graft selection criteria in section 5.2).

          7. Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%.

          8. 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

          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




1 Week - 22 Years

Accepts Healthy Volunteers



Joanne Kurtzberg, MD, , [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Joanne Kurtzberg, MD


 The Marcus Foundation

Study Sponsor

Joanne Kurtzberg, MD, Principal Investigator, Duke University

Verification Date

December 2021