Double Cord Blood TransplantPhase 1USBTXA127CBTNCT01300611
TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation
A Phase 1 study testing TXA127 300 mcg/kg/day and TXA127 1000 mcg/kg/day in people with Double Cord Blood Transplant and Acute Myelogenous Leukemia, run by Tarix Pharmaceuticals at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Double Cord Blood Transplant, Acute Myelogenous Leukemia, Myelodysplastic Syndrome
- What is being tested?
- TXA127 300 mcg/kg/day and TXA127 1000 mcg/kg/day
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Double Cord Blood Transplant, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Myelofibrosis, Acute Lymphoblastic Leukemia, Chronic Myelocytic Leukemia
- Being tested
- TXA127 300 mcg/kg/day, TXA127 1000 mcg/kg/day
- Keywords
- Double Cord Blood Transplantation, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Primary Myelofibrosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Non-Hodgkin, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TXA127 300 mcg/kg/dayDrug
Injection, 300 mcg/kg/day for 28 days
TXA127 1000 mcg/kg/dayDrug
Injection, 1000 mcg/kg/day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| TXA127 300 mcg/kg/day | Experimental | 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. Receives: Drug: TXA127 300 mcg/kg/day |
| TXA127 1000 mcg/kg/day | Experimental | 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. Receives: Drug: TXA127 1000 mcg/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 100 days post-transplantation
Secondary outcomes (5)
Platelet transfusion requirements
Platelet transfusion requirements based on units of platelets transfused and days of platelet transfusions
Measured: 100 days post-transplantation
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).
Measured: 100 days post-transplantation
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.
Measured: 100 days post-transplantation
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.
Measured: 100 days post-transplantation
Time to engraftment/recovery
Time to neutrophil engraftment and platelet recovery
Measured: 100 days post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2011 (estimated)
- Study startJan 2011
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Double Cord Blood TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tarix Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Constant Therapeutics LLC
- Responsible party
- Sponsor
- Investigators
- Uday R Popat, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300611
- Sponsor's protocol ID
- TXA127-2010-001
- Acronym
- USBTXA127CBT
- Status last verified
- Dec 2020
- First submitted
- 17 Feb 2011
- Last updated
- 8 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01300611
- Acronym / sponsor ID
- USBTXA127CBT / TXA127-2010-001
- Conditions
- Double Cord Blood Transplant, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Myelofibrosis, Acute Lymphoblastic Leukemia, Chronic Myelocytic Leukemia
- Keywords
- Double Cord Blood Transplantation, Neutrophil Engraftment, Platelet Engraftment, Immune Reconstitution, Mucositis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Tarix PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Constant Therapeutics LLC
- Study start
- Jan 2011
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 21 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TXA127 300 mcg/kg/day | Experimental | Drug: TXA127 300 mcg/kg/dayTreatment 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. |
| TXA127 1000 mcg/kg/day | Experimental | Drug: TXA127 1000 mcg/kg/dayTreatment 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TXA127 300 mcg/kg/dayInjection, 300 mcg/kg/day for 28 days | Drug | TXA127 300 mcg/kg/day |
| TXA127 1000 mcg/kg/dayInjection, 1000 mcg/kg/day for 28 days | Drug | TXA127 1000 mcg/kg/day |
Primary outcome
Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation
Time frame: 100 days post-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.
5 secondary outcomes
Platelet transfusion requirements
Time frame: 100 days post-transplantation
Immune reconstitution
Time frame: 100 days post-transplantation
Incidence, duration, and severity grade of mucositis
Time frame: 100 days post-transplantation
Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD)
Time frame: 100 days post-transplantation
Time to engraftment/recovery
Time frame: 100 days post-transplantation
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
Related trials for Double Cord Blood Transplant
RecruitingObservational study
Double Unit Cord Blood Transplant in Hematologic Malignancies.
Adult Double Unit Cord Blood Transplant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Uday R Popat, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TXA127 300 mcg/kg/day and TXA127 1000 mcg/kg/day in people with Double Cord Blood Transplant and Acute Myelogenous Leukemia, run by Tarix Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation (time frame: 100 days post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2020.