- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01882374
Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation
August 29, 2016 updated by: Tarix Pharmaceuticals
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
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 double umbilical cord blood transplantation (UCBT).
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.
Study Overview
Detailed Description
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.
Study Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia Cancer Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: SUPPORTIVE_CARE
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: TXA127, blood draws, physical exams
Single-arm safety/efficacy trial of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation for the treatment of hematologic malignancies.
Treatment dose is 300 mcg/kg/day TXA127.
|
Injection, 300mcg/kg/day for 28 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Grade II-IV acute graft-vs-host disease (aGVHD)
Time Frame: 100 days post-transplantation
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence, severity, and duration of mucositis
Time Frame: 100 days post-transplantation
|
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.
|
100 days post-transplantation
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Neutrophil engraftment and platelet recovery
Time Frame: 100 days post-transplantation
|
Time to initial neutrophil engraftment is defined as the number of days from infusion of UCB units 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 infusion of UCB units 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.
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100 days post-transplantation
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Platelet transfusion requirements
Time Frame: 100 days post-transplantation
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Platelet transfusion requirements are based on cumulative units of platelets transfused and cumulative days of platelet transfusions.
|
100 days post-transplantation
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Immune reconstitution
Time Frame: 100 days post-transplantation
|
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).
|
100 days post-transplantation
|
Duration of corticosteroid use
Time Frame: 100 days post-transplantation
|
Duration of corticosteroid use for GVHD will be summarized by frequency (i.e., number of days).
|
100 days post-transplantation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Mary J Laughlin, MD, University of Virginia
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2013
Primary Completion (ACTUAL)
December 1, 2013
Study Completion (ACTUAL)
December 1, 2013
Study Registration Dates
First Submitted
June 17, 2013
First Submitted That Met QC Criteria
June 17, 2013
First Posted (ESTIMATE)
June 20, 2013
Study Record Updates
Last Update Posted (ESTIMATE)
August 31, 2016
Last Update Submitted That Met QC Criteria
August 29, 2016
Last Verified
August 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TXA127-2012-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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