TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation (USBTXA127CBT)
The purpose of this study is to evaluate the effect of TXA127 on neutrophil and platelet counts in adult patients who have undergone a double cord blood transplant. The study will also evaluate the effect of TXA127 on chemotherapy-induced mucositis, an inflammation of the mucous membranes in the digestive tract (mouth to anus) and immune reconstitution which helps patients fight infections. For patients undergoing CBT, both neutrophil and platelet normalization and immune reconstitution can be delayed. TXA127 has shown to be well tolerated by patients and appears to induce a rapid production of neutrophils and platelets in the bloodstream as well as increase the immune system components. It has also been shown to reduce the severity of chemotherapy-induced mucositis.
Double Cord Blood Transplant
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelocytic Leukemia
Non Hodgkins Lymphoma
Chronic Lymphocytic Leukemia
Drug: TXA127 300 mcg/kg/day
Drug: TXA127 1000 mcg/kg/day
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||Phase I Evaluation of the Safety and Efficacy of TXA127 (Angiotensin 1-7) to Enhance Engraftment in Adults Undergoing Double Cord Blood Transplantation|
- Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: Yes ]The safety and tolerability profile of TXA127 will be provided by descriptively summarizing, at a minimum, the following outcomes: 1) number and proportion of patients with adverse events presented by preferred term, by system organ class (SOC), and by severity grade and relationship to TXA127, as assessed by the Investigator; 2) number and proportion of patients terminating TXA127 due to adverse events related to TXA127; 3) Day 100 treatment-related mortality (TRM) rate; 4) Day 100 mortality rate; 5) number of red blood cell and other blood component transfusions; 6) incidence of infection.
- Platelet transfusion requirements [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: No ]Platelet transfusion requirements based on units of platelets transfused and days of platelet transfusions
- Immune reconstitution [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: No ]Immune reconstitution will be assessed via the measurement of peripheral blood concentrations of CD3+, CD4+, CD8+, CD19+, and CD56+ cells (performed at Study Days 62 and 100).
- Incidence, duration, and severity grade of mucositis [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: No ]Incidence of mucositis is defined by the occurrence of least one adverse event with MedDRA preferred term that includes "mucositis" or "stomatitis". The severity grade will be determined by NCI-CTCAE.
- Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD) [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: No ]Incidence, severity and duration of aGVHD will be reported as a proportion (with 95% CIs) of subjects with Grade II-IV aGVHD. All incidents of aGVHD will at a minimum be listed, with the severity and time course included.
- Time to engraftment/recovery [ Time Frame: 100 days post-transplantation ] [ Designated as safety issue: No ]Time to neutrophil engraftment and platelet recovery
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: TXA127 300 mcg/kg/day
Treatment group 1 (300 mcg/kg/day) of a two-arm, dose-escalation pilot feasibility trial of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation for the treatment of a variety of hematologic malignancies for whom there is no available therapy with substantive anti-disease effect.
Drug: TXA127 300 mcg/kg/day
Injection, 300 mcg/kg/day for 28 days
Experimental: TXA127 1000 mcg/kg/day
Treatment group 2 (1000 mcg/kg/day) of a two-arm, dose-escalation pilot feasibility trial of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation for the treatment of a variety of hematologic malignancies for whom there is no available therapy with substantive anti-disease effect.
Drug: TXA127 1000 mcg/kg/day
Injection, 1000 mcg/kg/day for 28 days
Cord blood 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, one or two antigen-mismatched units are acceptable for transplantation. Despite these advantages, CB has a significant drawback which is that the number of hematopoietic stem cells obtained from a unit of CB is significantly lower than from a bone marrow (BM) harvest or peripheral blood stem cell (PBSC) harvest. Both engraftment and immune reconstitution are delayed in patients undergoing CB transplant. 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 time to neutrophil and platelet engraftment following transfusion of limited number of CD34+ cells.
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Uday R Popat, MD||M.D. Anderson Cancer Center|