Phase II Evaluation of the Efficacy of TXA127 (Angiotensin 1-7) to Reduce Acute Graft-vs-Host Disease in Adults Undergoing Double Umbilical Cord Blood Transplantation
Cord blood (CB) as a hematopoietic stem cell source has multiple advantages. Cord blood is
normally discarded at birth and can easily be collected and stored. Availability of numerous
CB banks has resulted in genetically diverse CB units including those from non-Caucasians.
Once a suitable CB unit is located, confirmatory typing can be quickly performed and a donor
unit can be shipped to the transplant center. Furthermore, because a CB graft results in a
lower incidence of graft-versus-host disease (GVHD), one or two antigen-mismatches may be
acceptable for transplantation. Despite these advantages, CB has a significant drawback:
the number of hematopoietic stem cells obtained from a unit of CB is significantly lower
than from a bone marrow (BM) or peripheral blood stem cell (PBSC) harvest. The number of
stem cells can be increased by transplanting two cord blood units, however the incidence of
GVHD increases in patients receiving two CB units compared to patients who receive one unit.
Another issue in this population is mucositis, as a result of myeloablative conditioning
given prior to the transplant, which can be debilitating to patients. TXA127 is
pharmaceutically-formulated angiotensin 1-7, a non-hypertensive derivative of angiotensin II
(which contains the 8th amino acid conferring receptor binding to blood pressure receptors).
TXA127 has multilineage effects on hematopoietic progenitors in vitro and in vivo. The
hematopoietic properties demonstrated in preclinical and clinical studies support the
investigation of TXA127 to reduce the incidence of acute GVHD (aGVHD) and mucositis in this
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Incidence of Grade II-IV acute graft-vs-host disease (aGVHD)
Incidence of Grade II-IV acute graft-vs-host disease (aGVHD) will be assessed using clinical staging and grading criteria as defined in Przepiorka et al. (1995). Duration and severity of aGVHD will also be evaluated.
100 days post-transplantation
Mary J Laughlin, MD
University of Virginia
United States: Food and Drug Administration
|University of Virginia Cancer Center||Charlottesville, Virginia 22908|