Using umbilical cord blood cells to treat inherited metabolic diseases
Augmentation of Umbilical Cord Blood Transplantation for Inherited Metabolic Diseases With Intrathecal Administration of Human Umbilical Cord Blood-Derived Oligodendrocyte-Like Cells
This study is testing if a new treatment using special cells from umbilical cord blood can help people with inherited metabolic diseases and early signs of nerve damage feel better when combined with standard cord blood transplants.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 1 Week to 22 Years |
| Sex | All |
| Sponsor | Duke University Academic / other |
| Drugs / interventions | chemotherapy, cyclophosphamide |
| Locations | 1 site (Durham, North Carolina) |
| Trial ID | NCT02254863 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and feasibility of administering DUOC-01, a type of oligodendrocyte-like cell derived from umbilical cord blood, through the intrathecal route in patients with inherited metabolic diseases who are also receiving standard umbilical cord blood transplantation. The study focuses on patients with early signs of demyelinating disease in the central nervous system, assessing both the safety of this new treatment and its efficacy as an adjunctive therapy. By potentially enhancing the engraftment of donor cells in the CNS, this approach seeks to improve neurological outcomes for affected patients.
Who should consider this trial
Good fit: Ideal candidates for this study are children and young adults aged 1 week to 21 years diagnosed with specific inherited metabolic diseases and showing neurological involvement.
Not a fit: Patients without evidence of neurological involvement or those outside the specified age range may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly slow or halt the progression of neurological deterioration in patients with certain inherited metabolic disorders.
How similar studies have performed: While this approach is innovative, similar studies involving umbilical cord blood transplantation have shown promise in treating other conditions, suggesting potential for success in this novel application.
Eligibility criteria
Show full 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
Where this trial is running
Durham, North Carolina
- Duke University Medical Center — Durham, North Carolina, United States (Recruiting)
Study contacts
- Principal investigator: Joanne Kurtzberg, MD — Duke University
- Study coordinator: Sydney Crane, RN
- Email: cordbloodtherapyinfo@dm.duke.edu
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.