TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation

NCT01300611 | Terminated Phase 1

• 1 other identifier: TXA127-2010-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  100 days post-transplantation

Secondary Outcomes (5)

• Platelet transfusion requirements

  100 days post-transplantation

• Immune reconstitution

  100 days post-transplantation

• Incidence, duration, and severity grade of mucositis

  100 days post-transplantation

• Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD)

  100 days post-transplantation

• Time to engraftment/recovery

  100 days post-transplantation

Study Arms (2)

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.

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.

Drug: TXA127 1000 mcg/kg/day

Interventions

TXA127 300 mcg/kg/day DRUG

Injection, 300 mcg/kg/day for 28 days

TXA127 300 mcg/kg/day

TXA127 1000 mcg/kg/day DRUG

Injection, 1000 mcg/kg/day for 28 days

TXA127 1000 mcg/kg/day

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Tarix Pharmaceuticals: lead
• Constant Therapeutics LLC: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

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; Mucositis

Interventions

angiotensin I (1-7)

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Leukemia, B-Cell; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Uday R Popat, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2011
• First Posted: February 21, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

US (1)