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Multiple Ascending Dose of BMS-911543

29 de julho de 2019 atualizado por: Bristol-Myers Squibb

A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BMS-911543 in Subjects With Myelofibrosis

The purpose of this first in human study is to determine if BMS-911543 is safe and tolerable in subjects with symptomatic intermediate-1, intermediate-2 or high risk myelofibrosis to permit clinical testing at the Maximum Tolerated Dose or at a Clinically Active Dose, and to determine if BMS-911543 will demonstrate efficacy in symptomatic myelofibrosis.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

98

Estágio

  • Fase 2
  • 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

  • Austrália
    • Victoria
      • East Melbourne, Victoria, Austrália, 3002
        • Local Institution
      • Melbourne, Victoria, Austrália, 3050
        • Local Institution
  • Estados Unidos
    • Minnesota
      • Rochester, Minnesota, Estados Unidos, 55905
        • Mayo Clinic
    • New York
      • New York, New York, Estados Unidos, 10029
        • The Mount Sinai School of Medicine
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • The University of Texas 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

  • Filho
  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Men and Women at least 18 years old
  • A diagnosis of symptomatic, primary or secondary Myelofibrosis (MF) [World Health Organization (WHO) 2008 criteria] with intermediate-1, intermediate-2 or high risk disease as assessed using the Dynamic International Prognostic Scoring System international prognostic scoring system
  • Last therapeutic or diagnostic treatment at least 28 days prior
  • Any toxicity from prior therapies must have resolved to Grade ≤1
  • Adequate Liver and Kidney Function
  • Serum amylase and lipase within normal institutional range
  • Platelet count ≥50,000 cell mm³
  • Absolute neutrophil count (ANC) ≥1,000 cells/mm3
  • Hemoglobin ≥8.0 g/dL

Exclusion Criteria:

  • Primary central nervous system tumors
  • Subjects with currently active malignancy (other than MF) or with a prior history of malignancy with the exception of: (i) adequately treated basal cell carcinoma of the skin, (ii) curatively treated in situ carcinoma of the cervix, (iii) other malignancy that has undergone potentially curative therapy with no evidence of disease recurrence ≥3 years
  • Any condition requiring chronic use of moderate/high dose steroids except inhalation or oral steroids for mild pulmonary disease
  • Splenic irradiation ≤3 months prior to treatment with study drug
  • Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or Human Immunodeficiency Virus-1 (HIV-1), or HIV-2 antibodies
  • Abnormalities in serum electrolytes
  • Significant cardiovascular disease
  • Current or recent gastrointestinal disease
  • Previous history of pancreatitis and/or significant risk factors for pancreatitis as judged by the treating physician
  • Evidence of uncontrolled active infection or active graft vs. host disease
  • Inability to tolerate oral medication

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: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Phase 1 (Cohort 1): BMS-911543 (5 mg)
BMS-911543 5 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 2): BMS-911543 (10 mg)
BMS-911543 10 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 3): BMS-911543 (20 mg)
BMS-911543 20 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 4): BMS-911543 (40 mg)
BMS-911543 40 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 5): BMS-911543 (80 mg)
BMS-911543 80 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 6): BMS-911543 (120 mg)
BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 7): BMS-911543 (160 mg)
BMS-911543 160 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 8): BMS-911543 (200 mg)
BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 9): BMS-911543 (240 mg)
BMS-911543 240 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 1 (Cohort 10): BMS-911543 (320 mg)
BMS-911543 320 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 2 (Cohort 11): BMS-911543 (120 mg)
BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2
Experimental: Phase 2 (Cohort 12): BMS-911543 (200 mg)
BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Medicamento: BMS-911543
Outros nomes:
  • Inibidor JAK2

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Number of Participants With Adverse Events
Prazo: From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).
From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
Number of Participants With Best Overall Response
Prazo: Day 1, at each returning on-treatment visit and the first post-treatment visit
Participants were clinically assessed for IWG-(International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia) defined response at each returning on-treatment visit and the first post-treatment visit. IWG-MRT criteria for best overall response are ordered high to low: CR>PR>CI>SD>PD>R where CR = Complete Remission, PR= Partial Remission, CI = Clinical Improvement, SD = Stable Disease, PD = Progressive Disease and R = Relapse. Best overall response is the best response of the subject during the treatment period or at the first post-treatment visit.
Day 1, at each returning on-treatment visit and the first post-treatment visit

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Prazo: Up to 6 months
JAK/STAT pathway activity will be evaluated by: 1) pSTATs levels using immunoassay; 2) expression levels of several JAK/STATs pathway genes. Whole blood will be collected at specific time-points. Due to portfolio/business decisions by the sponsor, the compound is no longer being developed and the study was terminated. Analysis was not completed because the study was terminated. This decision was not based on any safety concerns associated with BMS-911543.
Up to 6 months
Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmax Maximum observed plasma concentration
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmin (Trough observed (pre-dose) plasma concentration)
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Tmax = Time of maximum observed plasma concentration (Tmax) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (for Single Dose Period Only) (AUC(INF)) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC(INF) = Area under the plasma concentration-time curve from time zero extrapolated to infinite time (for single dose period only) (AUC(INF)) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration (for Single Dose Period Only) (AUC(0-T)) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (0-T) = Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration (for single dose period only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (TAU) = Area under the concentration-time curve in one dosing interval of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: T-HALF = The terminal-phase elimination half-life in plasma of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: CLT/F = Apparent total clearance (for parent compound only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Apparent Volume of Distribution After First Dosing Based on the Terminal Phase (for Parent Compound Only) (Vz/F) of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Vz/F = Apparent volume of distribution after first dosing based on the terminal phase (for parent compound only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Accumulation Index (AI): Ratio of AUC(TAU) on Day 15 to AUC(TAU) After the First Dose of BMS-911543 and it's Metabolite Met4
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Accumulation index (AI) = ratio of AUC(TAU) on Day 15 to AUC(TAU) after the first dose of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) After 1st Dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15 (AUC Ratio)
Prazo: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC Ratio = Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) after 1st dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Colaboradores e Investigadores

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

Patrocinador

Bristol-Myers Squibb

Publicações e links úteis

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Links úteis

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 (Real)

7 de abril de 2011

Conclusão Primária (Real)

19 de novembro de 2015

Conclusão do estudo (Real)

19 de novembro de 2015

Datas de inscrição no estudo

Enviado pela primeira vez

5 de novembro de 2010

Enviado pela primeira vez que atendeu aos critérios de CQ

5 de novembro de 2010

Primeira postagem (Estimativa)

7 de novembro de 2010

Atualizações de registro de estudo

Última Atualização Postada (Real)

31 de julho de 2019

Última atualização enviada que atendeu aos critérios de controle de qualidade

29 de julho de 2019

Última verificação

1 de julho de 2019

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Outros números de identificação do estudo

  • CA215-001

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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