Clinical trial NCT01882387: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hematologic Malignancies
Keywords: Allogeneic Peripheral Blood Stem Cell Transplantation
Graft-vs-Host Disease
Neutrophil Engraftment
Platelet Engraftment
Immune Reconstitution
Mucositis
Lead sponsor: Tarix Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-06-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Incidence of Grade II-IV acute graft-vs-host disease (aGVHD)
timeFrame: 100 days post-transplantation
Secondary outcomes:
measure: Incidence, duration, and severity grade of mucositis
timeFrame: 100 days post-transplantation
measure: Neutrophil engraftment and platelet recovery
timeFrame: 100 days post-transplantation
measure: Platelet transfusion requirements
timeFrame: 100 days post-transplantation
measure: Immune reconstitution
timeFrame: 100 days post-transplantation
measure: Duration of corticosteroid use
timeFrame: 100 days post-transplantation
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: St Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
Study officials:
affiliation: Emory University
name: Edmund K Waller, MD,PhD,FACP
role: PRINCIPAL_INVESTIGATOR
References: