Clinical Trial: Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: 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 Summary:

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 fo
Sponsor: Joanne Kurtzberg, MD

Current Primary Outcome:

  • 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: Same as current

Current Secondary Outcome:

  • 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: Same as current

Information By: Duke University

Dates:
Date Received: October 20, 2009
Date Started: October 2009
Date Completion:
Last Updated: April 3, 2017
Last Verified: April 2017