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Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation

Primary Purpose

Hematologic Malignancies

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

TXA127

About this trial

This is an interventional supportive care trial for Hematologic Malignancies focused on measuring Double Umbilical Cord Blood Transplantation, Acute Graft versus Host Disease, Neutrophil Engraftment, Platelet Recovery, Immune Reconstitution, Mucositis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Virginia 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 double cord blood transplantation for the treatment of hematologic malignancies. 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, severity, and duration 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 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.

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

NCT ID

NCT01882374

First Posted

June 17, 2013

Last Updated

August 29, 2016

Sponsor

Tarix Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01882374

Brief Title

Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation

Official Title

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

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

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 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies

Keywords

Double Umbilical Cord Blood Transplantation, Acute Graft versus Host Disease, Neutrophil Engraftment, Platelet Recovery, 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

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

Time Frame

100 days post-transplantation

Secondary Outcome Measure Information:

Title

Incidence, severity, and duration of mucositis

Description

Time Frame

100 days post-transplantation

Title

Neutrophil engraftment and platelet recovery

Description

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

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mary J Laughlin, MD

Organizational Affiliation

University of Virginia

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Virginia Cancer Center

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation

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