Total Body Irradiation With Fludarabine Conditioning Followed by Transplantation With Combined Umbilical Cord Blood Grafts
Results to date of umbilical cord blood transplantation in adult and fully mature adolescent
patients are inferior to what is seen in children. There are two reasons for this. First
is that the stem cell dose, measured in nucleated cells/kg body weight, is considerably
lower due to the size of the recipient. This results in a higher incidence of graft
failure, delayed engraftment, and impaired immune reconstitution. Multiple studies have
suggested that a nucleated cell dose below 1.5 to 2 x 107/kg results in an unacceptably high
risk for graft failure. Only a minority of adult patients will have a suitably matched
umbilical cord blood unit that contains more than 1.5 x 107 nucleated cells/kg. The second
reason for inferior outcome of umbilical cord blood transplantation in adult patients is
that in comparison to children, the conventional myeloablative bone marrow conditioning
regimens are more toxic. This phase 1 protocol will use a potentially less toxic bone
marrow conditioning regimen, followed by infusion of a combined umbilical cord blood graft
that will provide the patient with a higher stem cell dose than can be given with a single
umbilical cord blood infusion. The subjects will be conditioned with a TBI 13.5 Gy and
fludarabine. Fludarabine pharmacokinetics will be measured and correlated with the kinetics
of donor cell engraftment as well frequency of treatment-related toxicity. Following
conditioning, up to two unrelated, partially matched umbilical cord blood grafts will be
infused that will provide a minimum nucleated cell dose of 3 x 10e7/kg. The primary
objective of this study is to measure the frequency of treatment-related toxicity and
engraftment.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary objective will be to measure the time to and rate of hematologic engraftment following transplant and the frequency of treatment-related mortality.
3 years
Yes
Mitchell Horwitz, MD
Principal Investigator
Duke University Health System
United States: Institutional Review Board
Pro00009529
NCT00606437
September 2005
September 2014
Name | Location |
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Duke University Health System | Durham, North Carolina 27705 |