Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Digestive System Diseases

Mouth and Tooth Diseases

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Mucositis

Hematologic Diseases

Homologous Wasting Disease

Acute Graft Versus Host Disease

Antihypertensive Agents

Vasodilator Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Angiotensin I (1-7)

Angiotensin II

Angiotensinogen

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.

TXA127

Mary J Laughlin, MD

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.

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.

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

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

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.

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 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 are based on cumulative units of platelets transfused and cumulative days of platelet transfusions.

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 for GVHD will be summarized by frequency (i.e., number of days).

Tarix Pharmaceuticals

Symptoms and General Pathology

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Primary Myelofibrosis

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Marrow Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Chronic Myeloproliferative Disorders

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.

TXA127 300 mcg/kg/day

TXA127 1000 mcg/kg/day

Uday R Popat, MD

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.

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.

TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation

Phase I Evaluation of the Safety and Efficacy of TXA127 (Angiotensin 1-7) to Enhance Engraftment in Adults 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.

Platelet transfusion requirements based on units of platelets transfused and days of platelet transfusions

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 neutrophil engraftment and platelet recovery

Constant Therapeutics LLC

Nutritional and Metabolic Diseases

Metabolic Diseases

300mcg/kg/day, subcutaneous injection for up to 28 days

Kristin Page, MD

Joanne Kurtzberg, MD

Engraftment failure is a major obstacle to the success of cord blood transplantation in children with malignancies and inherited metabolic disorders, despite the fact that they receive relatively high doses of nucleated cells from UCB. TXA127 is pharmaceutically formulated Angiotensin 1-7 \[A(1-7)\], 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. Preclinical data show that TXA127 is a novel stimulator of early multilineage hematopoietic progenitors, increases engraftment of committed hematopoietic progenitors, and induces more rapid production of platelets and neutrophils in the peripheral circulation, especially in limited cell number transplants. Treatment with TXA127 following UCBT is expected to increase the numbers of hematopoietic progenitors and accelerate engraftment.

Evaluation of the Safety and Efficacy of TXA127 (Angiotensin 1-7) to Enhance Engraftment in Pediatric Patients Undergoing Single or Double Umbilical Cord Blood Transplantation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation	NCT01882374	Hematologic Mal...	TXA127	18 Years -	Tarix Pharmaceuticals
TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation	NCT01300611	Double Cord Blo... Acute Myelogeno... Myelodysplastic... Myelofibrosis Acute Lymphobla... Chronic Myelocy... Non Hodgkins Ly... Hodgkins Lympho... Chronic Lymphoc...	TXA127 300 mcg/... TXA127 1000 mcg...	18 Years - 60 Years	Tarix Pharmaceuticals
TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation	NCT01300611	Double Cord Blo... Acute Myelogeno... Myelodysplastic... Myelofibrosis Acute Lymphobla... Chronic Myelocy... Non Hodgkins Ly... Hodgkins Lympho... Chronic Lymphoc...	TXA127 300 mcg/... TXA127 1000 mcg...	18 Years - 60 Years	Tarix Pharmaceuticals
Evaluation of the Safety and Efficacy of TXA127 (Angiotensin 1-7) to Enhance Engraftment in Pediatric Patients Undergoing Single or Double Umbilical Cord Blood Transplantation	NCT01554254	Cord Blood Tran... Hematologic Mal... Inherited Metab...	TXA127	6 Months - 20 Years	Tarix Pharmaceuticals
Efficacy Study of a TXA127 to Reduce Acute Graft-vs-Host Disease in Subjects Undergoing Double Umbilical Cord Blood Transplantation	NCT01882374	Hematologic Mal...	TXA127	18 Years -	Tarix Pharmaceuticals

Spots Global Cancer Trial Database for neutrophil engraftment