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

Launched by JOANNE KURTZBERG, MD · Sep 29, 2014

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for children and young adults with certain inherited metabolic diseases, such as Adrenoleukodystrophy and Tay-Sachs Disease. The study aims to see if giving a specific type of cell (called DUOC-01) through the spine is safe and effective for patients who are also receiving a standard treatment called umbilical cord blood transplantation. The researchers want to learn more about how well this combination of treatments can help those with early signs of damage to their nervous system.

To participate in this trial, patients need to be between 1 week and 21 years old and have a confirmed diagnosis of one of the specified inherited metabolic diseases. They should show signs of neurological involvement, such as issues seen on brain scans or abnormal test results. Participants will receive the new treatment and be closely monitored for safety and effectiveness. It's important to note that this study is currently recruiting eligible participants, so it could provide a new option for families looking for additional treatment for these challenging conditions.

Gender

ALL

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 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