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Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases (IUHST-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01003912
Recruitment Status : Withdrawn (Patients were consented to screening but none were enrolled and proceeded with transplant.)
First Posted : October 29, 2009
Last Update Posted : June 29, 2017
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

Tracking Information
First Submitted Date  ICMJE October 20, 2009
First Posted Date  ICMJE October 29, 2009
Last Update Posted Date June 29, 2017
Study Start Date  ICMJE October 2009
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
  • To determine whether immune tolerance and donor cell engraftment can be achieved through first trimester injection of donor cells to fetus's diagnosed with lethal LSDs. [ Time Frame: after 3 patients ]
  • Safety and feasibility of fetal intrap. [ Time Frame: after 3 patients ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01003912 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
  • Donor chimerism for neonate at birth and 7 days post delivery. [ Time Frame: after 3 patients ]
  • Establishment of threshold enzyme levels in neonate at birth and 7 days post delivery. [ Time Frame: after 3 patients ]
  • Donor chimerism for mother post delivery and 1 year post date of birth. [ Time Frame: after 3 patients ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases
Official Title  ICMJE Treatment of Early Infantile-Onset Lysosomal Storage Diseases With Fetal Umbilical Cord Blood (UCB) Transplantation
Brief Summary The purpose of this study is to determine if it is safe to administer unrelated umbilical cord blood to pregnant women in their first trimester of pregnancy with a fetus that has a known diagnosis of certain lysosomal storage diseases. These diseases are known to cause severe and irreversible neurological disability in early infancy and which are lethal in childhood.
Detailed Description

The purpose of this study is to determine the safety of first trimester fetal stem cell therapy using unrelated donor partially HLA-matched stem and progenitor cells derived from human umbilical cord blood for the treatment of selected lysosomal storage diseases that are known to cause severe and irreversible neurological disability in early infancy and which are lethal in childhood.

This study is designed as a prospective phase I open-label single center trial. It is designed to asses the safety and feasibility of administration of ALD-601 UCB cells to first trimester fetuses known to be affected with a lethal lysosomal storage disease. The sample size is 12 patients enrolled in cohorts of size 3. Safety measures will be monitored by an independent DSMC in each of the 4 cohorts prior to proceeding to the next cohort.

Biological parents being considered for therapy will have HLA testing, mutation analysis for disease status, and psychological counseling. Mothers will have ultrasounds for gestational age and chorion villus testing for mutation analysis for Krabbe, MLD, Tay Sachs, Sandhoff, or PMD (whichever appropriate). A crown-rump length will be determined the day before the scheduled transfer. The fetal weight will be calculated from formula: Y (kg) = (2.9026 x 10-1) (X 2.6528). The estimated fetal weight at that gestational age would be about 0.5 ounces or 14 grams. A suitably matched unrelated umbilical cord blood will be identified and the 20% portion will be manipulated for the isolation of ALD-601 cells. ALD-601 (ALDHbr) cells are isolated by high speed flow sorting on the FACSAria (BD Biosciences). Upon completion of the sort, ALD-601 UCB cells are counted, viability is determined, and the cellular composition of the sample is measured by analytical flow cytometry using fluorescence antibodies to lineage marker for T-cells, granulocytes, monocytes, and erythrocytes. The content of ALDHbr cells is also confirmed by analytical flow cytometry. A dose of 1 x 105 - 2 x 106 cells/kg of estimated fetal weight is suspended in 300 microliters of Cellgenix Stem Cell Medium (CellGenix, Inc.). Release criteria will allow a maximum of 5 x 104 T cells/kg. If the sorted sample contains greater than 5 x 104 T cells/kg it is re-sorted using the FACSAria and re-evaluated for cell number, viability, and cellular content. Sterility testing will include Bac-T/ALERT cultures, endotoxin measurement (LAL), and gram stain. After meeting criteria for product release, ALD-601 is transported at 2-8 degree C in a validated cooler to Duke and released to the Stem Cell Laboratory. Duke personnel will transport the cooler containing the ALD-601 product to the ultrasound suite, where the medical team will allow the ALD-601 to warm briefly to room temperature prior to injection. Under continuous ultrasound guidance, a 22-gauge X 5 inch procedure needle will be used to puncture the fetal peritoneal cavity. 100 microliters of sterile saline will be instilled to confirm intraperitoneal placement. The stem cell infusion will then be injected through the needle followed by the injection of 200 microliters (dead space of the needle: 60 microliters) to displace all cells from the dead space of the needle. An ultrasound will be performed 24 hours later to confirm fetal viability. A subsequent ultrasound will be undertaken at 18 weeks gestation to confirm viability, assess detailed fetal anatomy and adequate serial fetal growth.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lysosomal Storage Diseases
  • Inborn Errors of Metabolism
Intervention  ICMJE Biological: ALD-601
ALD-601 is manufactured by Aldagen from the 20% compartment of the selected umbilical cord blood unit within 24 hrs of planned injection. A dose of ALD-601 that delivers 1 x 105 - 2 x 106 cells/kg of estimated fetal weight at day - 1 is suspended in 300 microliters of dialysis media.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 3, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2009)
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fetus with known enzymatic and, if possible, mutation diagnosis of selected lysosomal storage diseases, and history of enzymatic or mutation diagnosis of a previously affected family member.
  • Krabbe disease
  • Infantile metachromatic leukodystrophy disease (MLD)
  • Tay Sachs or Sandhoff (GM2 gangliosidoses) disease
  • Pelizaeus-Merzbacher disease (PMD).
  • Both parents have the "at risk" genotype
  • Both parents agree to psychological counseling prior to CVS
  • Both parents agree to delivery of subject at Duke University
  • Gestational age of < 9 weeks by sure menstrual dating or ultrasound of a natural pregnancy.
  • Singleton fetus
  • No evidence of abnormal nuchal thickening on preliminary ultrasound prior to chorion villus biopsy

Exclusion Criteria:

  • Pregnancy by in vitro fertilization
  • Evidence of a nuchal translucency of > 3.0 mm at the time of the ultrasound for the chorion villus biopsy.
  • HIV, hepatitis C or hepatitis B positive maternal status
  • Active infection in the mother at the time of scheduled CVS or cell injection as determined by clinical practice
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01003912
Other Study ID Numbers  ICMJE Pro00010188
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Joanne Kurtzberg, MD, Duke University
Study Sponsor  ICMJE Joanne Kurtzberg, MD
Collaborators  ICMJE Aldagen
Investigators  ICMJE
Principal Investigator: Joanne Kurtzberg, MD Duke University
PRS Account Duke University
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP