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
18 Years
N/A
Both
Hematologic Malignancies
Trial Information
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
patient population.
Inclusion Criteria:
- Provided written informed consent.
- ≥18 years of age.
- Meet institutional standard criteria for double UCB transplantation
- Myeloablative conditioning regimen
- Histologically confirmed diagnosis of a hematologic malignancy.
- Life expectancy of ≥4 months.
- Female subjects capable of reproduction (defined as a subject who has started menses)
must agree to the following: 1) Use of an effective oral or IM contraceptive method
during the course of the study and 2 months following the last administration of
Investigational Product; and 2) must have a negative pregnancy test result within 7
days prior to first Investigational Product dose.
Exclusion Criteria:
- Uncontrolled infection at the time of transplant.
- Pregnant or breastfeeding.
- Known to be seropositive for HIV or HTLV-1.
- Active CNS disease at the time of study enrollment.
- Treatment with an investigational agent within 30 days of anticipated administration
of the first dose of Investigational Product.
- Current alcohol use, illicit drug use or any other condition (e.g., psychiatric
disorder) that, in the opinion of the Investigator, may interfere with the subject's
ability to comply with the study requirements or visit schedule.
- Any co-morbid condition which, in the view of the Principal Investigators, renders
the subject at too high a risk from treatment complications and regimen-related
morbidity/mortality.
- Prophylactic treatment with palifermin for mucositis.
- Subjects with a known sensitivity to any of the Investigational Product components.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Incidence of Grade II-IV acute graft-vs-host disease (aGVHD)
Outcome Description:
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.
Outcome Time Frame:
100 days post-transplantation
Safety Issue:
No
Principal Investigator
Mary J Laughlin, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Virginia
Authority:
United States: Food and Drug Administration
Study ID:
TXA127-2012-01
NCT ID:
NCT01882374
Start Date:
January 2014
Completion Date:
September 2015
Related Keywords:
- Hematologic Malignancies
- Double Umbilical Cord Blood Transplantation
- Acute Graft versus Host Disease
- Neutrophil Engraftment
- Platelet Recovery
- Immune Reconstitution
- Mucositis
- Neoplasms
- Graft vs Host Disease
- Hematologic Neoplasms
Name | Location |
|---|---|
| University of Virginia Cancer Center | Charlottesville, Virginia 22908 |
