Researchers from the University of Pittsburgh and Gamida Cell announced that the University of Pittsburgh would be participating in an international multicenter Phase III study of StemEx® for the treatment of hematologic malignancies.[1] Details of this study can be accessed on the ExCell web site (www.stemexstudy.com). There are currently 15 U.S. centers and 11 centers in Europe and Israel participating in this study. This study is classified as a Phase III study but, because it is not randomized, patients will be compared to matched historical controls.

Umbilical cord blood is an acceptable source of stem cells for patients who lack a suitable unrelated stem cell donor. There is convincing evidence that the outcomes of children with leukemia receiving unrelated cord blood transplants are similar to those achieved with standard unrelated donor transplants. However, in both children and adults, the rate of recovery of marrow function is significantly prolonged compared with unrelated peripheral blood stem cell or bone marrow transplantation. Attempts to accelerate recovery of neutrophils and platelets include the infusion of in-vitro expanded cord blood stem cells and the infusion of two rather than one unrelated cord blood units.

Researchers from Gamida Cell have developed a proprietary method of expanding umbilical cord blood stem cells. This technology was granted orphan drug status in 2005 by the U.S. Food and Drug Administration (FDA). The current Phase III trial has been approved by the U.S. FDA.

This method uses the copper chelator tetraethylenepentamine (TEPA) to expand early progenitor cells ex vivo. Researchers from the M. D. Anderson Cancer Center have published the results of a Phase I/II study evaluating the engraftment of expanded cord blood.[2] In this study a fraction of an umbilical cord blood unit was expanded ex vivo. CD34+ umbilical cord blood hematologic precursors were cultured ex vivo with TEPA, stem cell factor, FLT 3 ligand, interleukin-6, thrombopoietin 6, and TEPA. Ten patients with advanced hematologic malignancies received high-dose treatment followed by infusion of the unmanipulated portion of the umbilical cord blood unit and the expanded portion. Nine patients engrafted with recovery of neutrophils in a median of 30 days and platelets in a median of 48 days. There were no cases of grade 3-4 graft-versus-host disease. The 100-day survival was 90%. This study showed the feasibility of this approach.

Comments: There has been a considerable effort over the past two decades to expand stem cells ex vivo for transplantation purposes. However, most studies have been equivocal at best in showing a benefit from expanded cells over infusion of unmanipulated stem cells. If Gamida is successful with the current study, it will be a first in this area of research.

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