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

7 de dezembro de 2020 atualizado por: Tarix Pharmaceuticals

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.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Antecipado)

20

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Estados Unidos
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • MD Anderson Cancer Center

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 60 anos (Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Cuidados de suporte
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: TXA127 300 mcg/kg/day
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.
Medicamento: TXA127 300 mcg/kg/day
Injection, 300 mcg/kg/day for 28 days
Experimental: TXA127 1000 mcg/kg/day
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.
Medicamento: TXA127 1000 mcg/kg/day
Injection, 1000 mcg/kg/day for 28 days

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Safety of TXA127 (Angiotensin 1-7) in subjects undergoing double cord blood transplantation
Prazo: 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.
100 days post-transplantation

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Reconstituição imune
Prazo: 100 dias após o transplante
A reconstituição imune será avaliada através da medição das concentrações sanguíneas periféricas de células CD3+, CD4+, CD8+, CD19+ e CD56+ (realizadas nos Dias de Estudo 62 e 100).
100 dias após o transplante
Incidence, duration, and severity grade of mucositis
Prazo: 100 days post-transplantation
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.
100 days post-transplantation
Platelet transfusion requirements
Prazo: 100 days post-transplantation
Platelet transfusion requirements based on units of platelets transfused and days of platelet transfusions
100 days post-transplantation
Incidence, duration, and severity grade of acute graft-vs-host-disease (aGVHD)
Prazo: 100 days post-transplantation
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.
100 days post-transplantation
Time to engraftment/recovery
Prazo: 100 days post-transplantation
Time to neutrophil engraftment and platelet recovery
100 days post-transplantation

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Tarix Pharmaceuticals

Colaboradores

Constant Therapeutics LLC

Investigadores

  • Investigador principal: Uday R Popat, MD, M.D. Anderson Cancer Center

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de janeiro de 2011

Conclusão Primária (Real)

1 de dezembro de 2020

Conclusão do estudo (Real)

1 de dezembro de 2020

Datas de inscrição no estudo

Enviado pela primeira vez

17 de fevereiro de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

17 de fevereiro de 2011

Primeira postagem (Estimativa)

21 de fevereiro de 2011

Atualizações de registro de estudo

Última Atualização Postada (Real)

8 de dezembro de 2020

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de dezembro de 2020

Última verificação

1 de dezembro de 2020

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • TXA127-2010-001

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