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

• Register: ClinicalTrials.gov
• Last refreshed on: 23 September 2024
• Main ID: NCT02254863
• Date of registration: 23/09/2014
• Prospective Registration: No
• Primary sponsor: Joanne Kurtzberg, MD
• Public title: UCB Transplant of Inherited Metabolic Diseases with Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells DUOC-01
• Scientific title: Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases with Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells
• Date of first enrolment: September 2014
• Target sample size: 40
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02254863
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Sydney Crane, RN

• Name: Joanne Kurtzberg, MD
• Affiliation: Duke University

• Name: Sydney Crane, RN

Key inclusion & exclusion 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 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


Age minimum: 1 Week
Age maximum: 22 Years
Gender: All

Health Condition(s) or Problem(s) studied

Mucopolysaccharidosis II

Leukodystrophy, Globoid Cell

Sandhoff Disease

Alpha-Mannosidosis

Neimann Pick Disease

Sanfilippo Mucopolysaccharidoses

Tay-Sachs Disease

Pelizaeus-Merzbacher Disease

Adrenoleukodystrophy

Batten Disease

Brain Diseases, Metabolic, Inborn

Leukodystrophy, Metachromatic

Intervention(s)

Biological: DUOC-01

Primary Outcome(s)

Evaluate for Neuro Toxicity [Time Frame: 1 month after infusion]

Evaluate for Infusional Toxicity [Time Frame: 24 hours after infusion]

Secondary Outcome(s)

Efficacy determination [Time Frame: 1-5 years]

Secondary ID(s)

Pro00050198

Source(s) of Monetary Support

Please refer to primary and secondary sponsors