ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases

Study Overview
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Brief Summary
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Eligible research subjects will receive an unrelated umbilical cord blood transfusion as a possible cure for their inherited metabolic disease. A portion of cord blood cells (ALD-101) will be separated from the cord blood unit and given approximately 4 hours after the standard cord blood transfusion. The study will test if the supplemental cells will increase the speed at which normal levels of circulating blood cells are re-established after transplant.

Detailed Description
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Subjects will be hospitalized and undergo high doses of chemotherapy which will destroy the child's normal cells including their bone marrow (which forms blood cells) in order to prepare their body for the umbilical cord blood transplant. The cord blood transplant is intended to rescue your child's bone marrow from the bad effects of the procedure. The child will receive 80% of a standard cord blood transplant followed by 20% supplemental stem cell called ALD-101. The study will evaluate if these cells (ALD-101) will repopulate the bone marrow more rapidly after transplant. This would shorten the period of time that the transplanted subject would be at risk for infection and bleeding and would also decrease the number of red blood cell and platelet transfusions needed. ALD-101 has been used as a supplement to cord blood transplant in twenty-eight children with genetic diseases and malignancy in one previous clinical study that is on-going. The main purpose of this research study is to test whether a portion of cord blood cells that have been separated from a cord blood unit (ALD-101) will increase the speed at which normal levels of circulating blood cells are re-established after transplant. This is the experimental part of this study. ALD-101 is also being tested to see if it is safe.

Official Title
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A Phase III Trial of ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transplantation (UCBT) in Patients With Inborn Errors of Metabolism

Conditions
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Inherited Metabolic Diseases, Lysosomal Storage Disorders, Peroxisomal Storage Diseases, Inborn Errors of Metabolism, Mucopolysaccharidosis

Intervention / Treatment
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* Biological: ALD-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis of inherited metabolic diseases; including the following: Hurler Syndrome (MPS I) Hurler-Scheie Syndrome Hunter Syndrome (MPS II) Sanfilippo Syndrome A and B(MPS III) Maroteaux-Lamy Syndrome (MPS VI) Krabbe Disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Adrenoleukodystrophy (ALD and AMN) Sandhoff Disease Tay Sachs Disease Pelizaeus Merzbacher (PMD) Niemann-Pick Disease Alpha-mannosidosis I-Cell Disease (ML II) Fucosidosis GM I Gangliosidosis Canavan Disease must be <16 years of age at the time of study enrollment must have a good performance status (Lansky ≥80%) must have adequate function of other organ systems including: kidney, liver, heart and lungs must have given valid written informed consent must have a minimum life expectancy of at least 6 months must be determined to be a good candidate for a standard umbilical cord blood transplant must have an IQ >70 or if too young for IQ testing the potential to reach this endpoint by age 5 Exclusion Criteria: HIV, Hepatitis B and/or Hepatitis C positive concurrently involved in any other clinical study that affects engraftment or immune reconstitution uncontrolled seizures, apnea, evidence of aspiration pneumonia, or evidence of brain stem involvement uncontrolled infections prior allogeneic stem cell transplant with cytoreduction preparative therapy within 12 months of enrollment

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br> | Biological: ALD-101<br>* A subpopulation of cord blood cells composed of cells that express a high level of the intracellular enzyme aldehyde dehydrogenase (ALDH).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of adjuvant therapy of ALD-101 in accelerating platelet engraftment in patients also receiving a standard unrelated UCBT for treatment of inherited metabolic diseases |  | 180 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of ALD-101 in accelerating neutrophil engraftment |  | 180 Days | 
| To assess the safety of adjuvant therapy of ALD-101 in infusional toxicity, adverse events, and primary graft failure. |  | 180 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS III, Hurler Syndrome, MPS I, Hurler-Scheie Syndrome, Hunter Syndrome, MPS II, Sanfilippo Syndrome, Maroteaux-Lamy Syndrome, MPS VI, Krabbe Disease, Globoid Leukodystrophy, Metachromatic Leukodystrophy, MLD, Adrenoleukodystrophy, ALD, Adrenomyeloneuropathy, AMN, Sandhoff Disease, Tay Sachs Disease, Pelizaeus Merzbacher, PMD, Niemann-Pick Disease A, Niemann-Pick Disease B, Alpha-mannosidosis, Inherited metabolic diseases, Inborn errors of metabolism, Lysosomal storage diseases, Peroxisomal storage diseases, Hematopoietic stem cell transplantation, Umbilical cord blood transplantation, Mucopolysaccharidosis, Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis III, Mucopolysaccharidosis VI, I Cell disease, Fucosidosis, GM1 Gangliosidosis, Canavan Disease