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

Primary Purpose

Adrenoleukodystrophy, Batten Disease, Mucopolysaccharidosis II

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

DUOC-01

About this trial

This is an interventional treatment trial for Adrenoleukodystrophy focused on measuring Adrenoleukodystrophy, Batten Disease, Hunter Syndrome, Krabbe, Metachromatic Leukodystrophy, ALD, MLD, PMD

Eligibility Criteria

1 Week - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
  - 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.
Patients must not have a suitable fully matched, non-carrier sibling or related bone marrow donor.
Patients must have an available, suitably matched, banked UCB unit in a two-compartment configuration (see graft selection criteria in section 5.2).
Patients must have a performance status as follows: Lansky ≥ 40%, or Karnofsky ≥ 40%.
Patients must have a life expectancy of ≥ 6 months.

Exclusion Criteria:

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

Sites / Locations

Duke University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intrathecal administration of DUOC-01

Arm Description

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

Outcomes

Primary Outcome Measures

Evaluate for Infusional Toxicity

Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness

Evaluate for Neuro Toxicity

Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02254863

First Posted

September 23, 2014

Last Updated

September 26, 2023

Sponsor

Joanne Kurtzberg, MD

Collaborators

The Marcus Foundation

1. Study Identification

Unique Protocol Identification Number

NCT02254863

Brief Title

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

Acronym

DUOC-01

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 2014 (undefined)

Primary Completion Date

October 2024 (Anticipated)

Study Completion Date

October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Joanne Kurtzberg, MD

Collaborators

The Marcus Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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 may be derived from the same UCB donor unit, or a second UCB donor unit will be used to manufacture the DUOC-01 cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intrathecal administration of DUOC-01

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

DUOC-01

Intervention Description

Intrathecal administration of DUOC-01

Primary Outcome Measure Information:

Title

Evaluate for Infusional Toxicity

Description

Will monitor for fever, vomiting, neck stiffness, seizures, changes in state of consciousness

Time Frame

24 hours after infusion

Title

Evaluate for Neuro Toxicity

Description

Perform computerized tomography (CT) scan to evaluate for bleeding, tumor formation, central nervous system generalized infiltration

Time Frame

1 month after infusion

Secondary Outcome Measure Information:

Title

Efficacy determination

Description

Time Frame

1-5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Week

Maximum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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. 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% Patients must have a life expectancy of ≥ 6 months. Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sydney Crane, RN

cordbloodtherapyinfo@dm.duke.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Erin Arbuckle

cordbloodtherapyinfo@dm.duke.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joanne Kurtzberg, MD

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27705

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sydney Crane, RN

cordbloodtherapyinfo@dm.duke.edu

First Name & Middle Initial & Last Name & Degree

Joanne Kurtzberg, MD

First Name & Middle Initial & Last Name & Degree

Jessica Sun, MD

12. IPD Sharing Statement

Learn more about this trial

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

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