Clinical trial NCT00654433: ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases
Official title: A Phase III Trial of ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transplantation (UCBT) in Patients With Inborn Errors of Metabolism
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Inherited Metabolic Diseases
Lysosomal Storage Disorders
Peroxisomal Storage Diseases
Inborn Errors of Metabolism
Mucopolysaccharidosis
Keywords: Hurler Syndrome
MPS I
Hurler-Scheie Syndrome
Hunter Syndrome
MPS II
Sanfilippo Syndrome
MPS III
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
Lead sponsor: Aldagen
Sponsor class: INDUSTRY
First posted: 2008-04-08
Enrollment: 40
Sex: ALL
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 180 Days
Secondary outcomes:
measure: To assess the efficacy of ALD-101 in accelerating neutrophil engraftment
timeFrame: 180 Days
measure: To assess the safety of adjuvant therapy of ALD-101 in infusional toxicity, adverse events, and primary graft failure.
timeFrame: 180 Days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mattel Children's Hospital at UCLA
state: California
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Aldagen
name: James Hinson, MD
role: STUDY_DIRECTOR
affiliation: Duke University
name: Joanne Kurtzberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prasad VK, Kurtzberg J. Emerging trends in transplantation of inherited metabolic diseases. Bone Marrow Transplant. 2008 Jan;41(2):99-108. doi: 10.1038/sj.bmt.1705970. Epub 2008 Jan 7.
citation: Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, Wagner JE, Kurtzberg J. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb;12(2):184-94. doi: 10.1016/j.bbmt.2005.09.016.
citation: Escolar ML, Poe MD, Martin HR, Kurtzberg J. A staging system for infantile Krabbe disease to predict outcome after unrelated umbilical cord blood transplantation. Pediatrics. 2006 Sep;118(3):e879-89. doi: 10.1542/peds.2006-0747. Epub 2006 Aug 21.
citation: Gentry T, Deibert E, Foster SJ, Haley R, Kurtzberg J, Balber AE. Isolation of early hematopoietic cells, including megakaryocyte progenitors, in the ALDH-bright cell population of cryopreserved, banked UC blood. Cytotherapy. 2007;9(6):569-76. doi: 10.1080/14653240701466347.