Back to resultsEfficacy Study of a TXA127 to Reduce Graft-vs-Host Disease in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
Primary Purpose
Hematologic Malignancies
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TXA127
Sponsored by
About this trial
This is an interventional supportive care trial for Hematologic Malignancies focused on measuring Allogeneic Peripheral Blood Stem Cell Transplantation, Graft-vs-Host Disease, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis
Eligibility Criteria
Inclusion Criteria:
- Provided written informed consent.
- ≥18 years of age.
- Meet institutional standard criteria for PBSC 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.
Sites / Locations
- Winship Cancer Institute, Emory University
- Siteman Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TXA127, blood draws, physical exams
Arm Description
Single-arm safety/efficacy trial of TXA127 (Angiotensin 1-7) in subjects undergoing allogeneic peripheral blood stem cell transplantation for the treatment of a variety of hematologic malignancies for whom there is no available therapy with substantive anti-disease effect. Treatment dose is 300 mcg/kg/day TXA127.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Incidence, duration, and severity grade of mucositis
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.
Neutrophil engraftment and platelet recovery
Time to initial neutrophil engraftment is defined as the number of days from PBSC transplant to the first of 3 consecutive days of an ANC ≥0.5 × 10^9/L. Time to initial platelet recovery is defined as the number of days from PBSC transplant to the first of 3 consecutive platelet count measurements tested on different days with a count ≥20 × 10^9/L with no platelet transfusion in the prior 7 days.
Platelet transfusion requirements
Platelet transfusion requirements are based on cumulative units of platelets transfused and cumulative days of platelet transfusions.
Immune reconstitution
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).
Duration of corticosteroid use
Duration of corticosteroid use for GVHD will be summarized by frequency (i.e., number of days).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01882387
Brief Title
Efficacy Study of a TXA127 to Reduce Graft-vs-Host Disease in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
Official Title
Phase II Evaluation of the Efficacy of TXA127 (Angiotensin 1-7) to Reduce Acute Graft-vs.-Host Disease in Adults Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Change in drug product development strategy
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tarix Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of TXA127 to reduce the incidence (Grade II-IV) of acute Graft-vs.-Host Disease (aGVHD) in adult subjects undergoing allogeneic peripheral blood stem cell transplantation (PBSCT). The study will also evaluate the effects of TXA127 on incidence, severity and duration of mucositis; neutrophil engraftment and platelet recovery; platelet transfusion requirements; immune reconstitution; and duration of corticosteroid use. TXA127 has shown to be well tolerated by patients and appears to induce rapid production of neutrophils and platelets in the bloodstream, as well as increase the immune system components. TXA127 has also been shown reduce the severity of chemotherapy-induced mucositis.
Detailed Description
Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as an effective treatment for malignant disease. The three most common sources for stem cells used in HSCT are bone marrow (BM), umbilical cord blood (UCB), and peripheral blood stem cells (PBSC). In a retrospective review of 1,525 adults with acute leukemia receiving allogeneic transplants between 2002 and 2006, UCB accounted for 10.8%, PBSC for 58.2%, and BM for 31% of the population (Eapen et al., 2010). PBSC as a source of hematopoietic stem cells for transplantation has advantages over bone marrow in terms of donation ease and comfort and over cord blood in terms of adequate cell dose. However, PBSC transplantations are associated with an increased incidence of graft-versus-host disease (GVHD). Based on current literature acute GVHD (aGVHD) is reported in 48-80% of PBSCT recipients (Eapen et al., 2010, Ferrara et al., 2009). Additionally, the myeloablative conditioning regimens used for these transplants often result in mucositis which can be debilitating to patients. TXA127 is pharmaceutically-formulated angiotensin 1-7, a non-hypertensive derivative of angiotensin II. 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 aGVHD and mucositis in this patient population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Allogeneic Peripheral Blood Stem Cell Transplantation, Graft-vs-Host Disease, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TXA127, blood draws, physical exams
Arm Type
Experimental
Arm Description
Single-arm safety/efficacy trial of TXA127 (Angiotensin 1-7) in subjects undergoing allogeneic peripheral blood stem cell transplantation for the treatment of a variety of hematologic malignancies for whom there is no available therapy with substantive anti-disease effect. Treatment dose is 300 mcg/kg/day TXA127.
Intervention Type
Drug
Intervention Name(s)
TXA127
Intervention Description
Injection, 300mcg/kg/day for 28 days
Primary Outcome Measure Information:
Title
Incidence of Grade II-IV acute graft-vs-host disease (aGVHD)
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.
Time Frame
100 days post-transplantation
Secondary Outcome Measure Information:
Title
Incidence, duration, and severity grade of mucositis
Description
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.
Time Frame
100 days post-transplantation
Title
Neutrophil engraftment and platelet recovery
Description
Time to initial neutrophil engraftment is defined as the number of days from PBSC transplant to the first of 3 consecutive days of an ANC ≥0.5 × 10^9/L. Time to initial platelet recovery is defined as the number of days from PBSC transplant to the first of 3 consecutive platelet count measurements tested on different days with a count ≥20 × 10^9/L with no platelet transfusion in the prior 7 days.
Time Frame
100 days post-transplantation
Title
Platelet transfusion requirements
Description
Platelet transfusion requirements are based on cumulative units of platelets transfused and cumulative days of platelet transfusions.
Time Frame
100 days post-transplantation
Title
Immune reconstitution
Description
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).
Time Frame
100 days post-transplantation
Title
Duration of corticosteroid use
Description
Duration of corticosteroid use for GVHD will be summarized by frequency (i.e., number of days).
Time Frame
100 days post-transplantation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provided written informed consent.
≥18 years of age.
Meet institutional standard criteria for PBSC 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edmund K Waller, MD,PhD,FACP
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Siteman Cancer Center
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Efficacy Study of a TXA127 to Reduce Graft-vs-Host Disease in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
We'll reach out to this number within 24 hrs