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TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation (USBTXA127CBT)

Primary Purpose

Double Cord Blood Transplant, Acute Myelogenous Leukemia, Myelodysplastic Syndrome

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TXA127 300 mcg/kg/day
TXA127 1000 mcg/kg/day
Sponsored by
Tarix Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Double Cord Blood Transplant focused on measuring Double Cord Blood Transplantation, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects with Acute Myelogenous Leukemia (AML) past first remission, in first or subsequent relapse, induction failure, or in first remission with high-risk for relapse (with high-risk cytogenetics or presence of flt3 mutation or secondary leukemia from prior chemotherapy)
  • Myelodysplastic Syndrome or Myelofibrosis of intermediate or high-risk
  • Acute Lymphoblastic Leukemia (ALL): Induction failure, fist complete remission with Philadelphia chromosome or translocation (4:11), hypodiploidy and or evidence of minimal residual disease by flow cytometry, second or third complete remission or second relapse
  • Chronic Myelocytic leukemia (CML): Second chronic phase or accelerated phase
  • Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission or relapse
  • Hodgkin's Lymphoma (HL): Induction failures, second or third complete remission or relapse
  • Chronic Lymphocytic leukemia (CLL): Progressive disease following standard therapy
  • Other hematologic malignancies which meet investigational site standards for cord blood transplant
  • Subjects must be at least 18 years of age
  • Subjects must have ECOG status of ≤ 2
  • Subjects with bone marrow blasts ≤ 10%
  • Subjects must have adequate major organ function
  • Male and Female Subjects capable of reproduction must agree to use contraceptive methods during the course of the study and for 2 months following the last administration of study drug
  • Cord blood requirements: a) Unrelated CB will be used as a source of hematopoietic support if a 7/8 or 8/8 related or 8/8 unrelated bone marrow donor is not available, or if the tempo of the subject's disease dictates it is not in the subject's best interest to wait for an unrelated marrow donor to be procured. b) Subjects must have two CB units available which are matched with the subject at 4/6, 5/6, or 6/6 HLA class I (serological) and II (molecular) antigens. Each unit must contain at least 1 x 10^7 total nucleated cells/kg recipient body weight (pre-thaw).

Exclusion Criteria:

  • Subjects who received antineoplastic treatment including chemotherapy, immunotherapy and radiation therapy ≤ 2 weeks prior to Screening Period
  • Subjects who underwent prior total body irradiation
  • Subjects who received prior allogeneic hematopoietic cell transplants
  • Subjects seropositive for HIV, Hepatitis B or Hepatitis C
  • Female subjects who are pregnant or breastfeeding
  • Subjects who have received an investigational drug within 30 days of projected first administration of study drug (Day 0)
  • Subjects with 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
  • Subjects with known hypersensitivity to TXA127
  • Subjects with uncontrolled medical or psychiatric condition which would limit informed consent
  • Subjects with a willing and appropriate HLA-matched related marrow donor

Sites / Locations

  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

TXA127 300 mcg/kg/day

TXA127 1000 mcg/kg/day

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation
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.

Secondary Outcome Measures

Platelet transfusion requirements
Platelet transfusion requirements based on units of platelets transfused and 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).
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.
Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD)
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 to neutrophil engraftment and platelet recovery

Full Information

First Posted
February 17, 2011
Last Updated
December 7, 2020
Sponsor
Tarix Pharmaceuticals
Collaborators
Constant Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01300611
Brief Title
TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation
Acronym
USBTXA127CBT
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Study Start Date
January 2011 (undefined)
Primary Completion Date
December 2020 (Actual)
Study Completion Date
December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tarix Pharmaceuticals
Collaborators
Constant Therapeutics LLC

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Double Cord Blood Transplant, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Myelofibrosis, Acute Lymphoblastic Leukemia, Chronic Myelocytic Leukemia, Non Hodgkins Lymphoma, Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
Keywords
Double Cord Blood Transplantation, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TXA127 300 mcg/kg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
TXA127 1000 mcg/kg/day
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TXA127 300 mcg/kg/day
Intervention Description
Injection, 300 mcg/kg/day for 28 days
Intervention Type
Drug
Intervention Name(s)
TXA127 1000 mcg/kg/day
Intervention Description
Injection, 1000 mcg/kg/day for 28 days
Primary Outcome Measure Information:
Title
Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation
Description
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.
Time Frame
100 days post-transplantation
Secondary Outcome Measure Information:
Title
Platelet transfusion requirements
Description
Platelet transfusion requirements based on units of platelets transfused and 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
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
Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD)
Description
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 Frame
100 days post-transplantation
Title
Time to engraftment/recovery
Description
Time to neutrophil engraftment and platelet recovery
Time Frame
100 days post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with Acute Myelogenous Leukemia (AML) past first remission, in first or subsequent relapse, induction failure, or in first remission with high-risk for relapse (with high-risk cytogenetics or presence of flt3 mutation or secondary leukemia from prior chemotherapy) Myelodysplastic Syndrome or Myelofibrosis of intermediate or high-risk Acute Lymphoblastic Leukemia (ALL): Induction failure, fist complete remission with Philadelphia chromosome or translocation (4:11), hypodiploidy and or evidence of minimal residual disease by flow cytometry, second or third complete remission or second relapse Chronic Myelocytic leukemia (CML): Second chronic phase or accelerated phase Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission or relapse Hodgkin's Lymphoma (HL): Induction failures, second or third complete remission or relapse Chronic Lymphocytic leukemia (CLL): Progressive disease following standard therapy Other hematologic malignancies which meet investigational site standards for cord blood transplant Subjects must be at least 18 years of age Subjects must have ECOG status of ≤ 2 Subjects with bone marrow blasts ≤ 10% Subjects must have adequate major organ function Male and Female Subjects capable of reproduction must agree to use contraceptive methods during the course of the study and for 2 months following the last administration of study drug Cord blood requirements: a) Unrelated CB will be used as a source of hematopoietic support if a 7/8 or 8/8 related or 8/8 unrelated bone marrow donor is not available, or if the tempo of the subject's disease dictates it is not in the subject's best interest to wait for an unrelated marrow donor to be procured. b) Subjects must have two CB units available which are matched with the subject at 4/6, 5/6, or 6/6 HLA class I (serological) and II (molecular) antigens. Each unit must contain at least 1 x 10^7 total nucleated cells/kg recipient body weight (pre-thaw). Exclusion Criteria: Subjects who received antineoplastic treatment including chemotherapy, immunotherapy and radiation therapy ≤ 2 weeks prior to Screening Period Subjects who underwent prior total body irradiation Subjects who received prior allogeneic hematopoietic cell transplants Subjects seropositive for HIV, Hepatitis B or Hepatitis C Female subjects who are pregnant or breastfeeding Subjects who have received an investigational drug within 30 days of projected first administration of study drug (Day 0) Subjects with 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 Subjects with known hypersensitivity to TXA127 Subjects with uncontrolled medical or psychiatric condition which would limit informed consent Subjects with a willing and appropriate HLA-matched related marrow donor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uday R Popat, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation

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