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Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia

2 de março de 2017 atualizado por: Pfizer

An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia

The Phase 1 portion of this study will assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule. The Phase 2 portion of the study will evaluate the efficacy of inotuzumab ozogamicin as measured by hematologic remission rate (CR + CRi) in patients in second or later salvage status.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

72

Estágio

  • Fase 2

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
    • California
      • Duarte, California, Estados Unidos, 91010-3000
        • City of Hope National Medical Center
      • Palo Alto, California, Estados Unidos, 94304
        • Stanford Unversity Cancer Clinical Trials Office
      • Palo Alto, California, Estados Unidos, 94304
        • Stanford Unversity Hospital and Clinics, CTRU
      • Stanford, California, Estados Unidos, 94305
        • Stanford Cancer Institute
      • Stanford, California, Estados Unidos, 94305
        • Stanford University Hospital and Clinics
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60637
        • The University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Estados Unidos, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, Estados Unidos, 02114
        • Massachusetts General Hospital (MGH)
      • Boston, Massachusetts, Estados Unidos, 02115
        • Brigham and Women's Hospital (BWH)
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48201
        • Karmanos Cancer Institute
      • Farmington Hills, Michigan, Estados Unidos, 48334
        • Karmanos Cancer Institute at Farmington Hills
    • Ohio
      • Cleveland, Ohio, Estados Unidos, 44195
        • Cleveland Clinic
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, Estados Unidos, 98109
        • Seattle Cancer Care Alliance

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 e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). Subjects enrolled in the Phase 2 portion of the study must be due to receive salvage 2 or later therapy.
  • Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
  • Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

  • Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia.
  • Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry.
  • Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

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
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Inotuzumab Ozogamicin
Medicamento: Inotuzumab Ozogamicin

Part 1: Administered intravenously as 2 - 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total dose per cycle 0.8 mg/m^2 to 2.0 mg/m^2.

Part 2 Expansion and Part 3 Phase 2: Administered intravenously as 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total initial dose per cycle 1.8 mg/m^2.

Outros nomes:
  • CMC-544

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase
Prazo: Cycle 1
DLT was any of the following in the first cycle & attributable to inotuzumab ozogamicin: any greater than or equal to (≥) Grade 4 non-hematologic toxicity except nausea/vomiting (if manageable with supportive care), alopecia, & toxicities secondary to neutropenia & sepsis; prolonged myelosuppression (absolute neutrophil count [ANC] less than [<] 500 per microliter [/µL] or platelet count <25,000/µL in bone marrow with <5 percent (%) blasts & no evidence of leukemia more than 45 days beyond the most recent dose of test article); any Grade 3 non-hematologic toxicity (excluding toxicities such as alopecia or those secondary to neutropenia & sepsis) not resolving to ≥ Grade 2 within 7 days of the most recent dose of test article or was clinically significant irrespective of duration; any ≥ Grade 3 elevation of alanine aminotransferase, aspartate aminotransferase or bilirubin lasting ≥7 days; any test article related toxicity resulting in permanent discontinuation of test article.
Cycle 1
Percentage of Participants With Preliminary Satisfactory Response (Complete Response [CR], CR With Incomplete Count Recovery [CRi], Partial Response [PR], or Resistant Disease [RD]) Indicating Disease Stability After First Dose During Phase 1 Dose-Finding
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was the disappearance of leukemia indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was as for CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was an improved or no worsening of acute lymphocytic leukemia indicated by no peripheral blood blasts, and/or at least a 50% decrease in the marrow blast percentage, compared to pre-treatment value, and marrow blast percentage ≥5% and less than or equal to (≤)25% and/or C2 extramedullary disease status. RD occurred if a participant survived ≥7 days following completion of initial treatment course and had persistent leukemia in the most recent peripheral blood smear or bone marrow and/or persistent disease involvement at any extramedullary site after completion of therapy.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR or CRi During Phase 2
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR, CRi or PR During the Phase 1 Expansion Phase
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
From screening to progressive disease or another induction therapy started, up to approximately 2 years

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Percentage of Participants With CR, CRi or PR in Phase 2
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL. PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Number of Participants With Minimal Residual Disease (MRD) Negativity in Participants Achieving CR and CRi
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
MRD negativity was defined as <0.01% mononuclear cells.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants With CR or CRi by Cytogenetic Category
Prazo: From screening to progressive disease or another induction therapy started, up to approximately 2 years
CR was defined as a disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC <1000/µL and/or platelets <100,000/µL.
From screening to progressive disease or another induction therapy started, up to approximately 2 years
Percentage of Participants Who Had a Post-Treatment Stem-Cell Transplant (SCT)
Prazo: Up to approximately 2 years from first dose
Post-treatment SCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin.
Up to approximately 2 years from first dose
Progression Free Survival (PFS)
Prazo: Up to approximately 2 years from first dose
PFS was defined as the time from Cycle 1 Day 1 to first documentation of PFS event (earliest date of objective progression [PD], treatment discontinuation due to global deterioration of health status, subsequent induction or transplant after best response of PR or resistant disease, relapse after CR or CRi, or death due to any cause). Participants last known to be 1) alive and 2) without a PFS event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Duration of Remission (DoR1) for Participants Who Achieved CR or CRi
Prazo: Up to approximately 2 years from first dose
DoR1 was defined for participants who responded as the time from the date of first documentation of Complete Hematologic Response (CR or CRi) to the date of the first documentation of relapse after CR or CRi, treatment discontinuation due to global deterioration of health status) or to death due to any cause. Participants last known to be 1) alive and 2) without a DoR1 event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Duration of Response (DoR) for Participants Who Achieved CR/CRi or PR
Prazo: Up to approximately 2 years from first dose
DoR was defined for participants who respond as the time from the date of first documentation of Hematologic Response (CR, CRi, or PR) to the date of the first documentation of DoR event (earliest date of PD, treatment discontinuation due to global deterioration of health status, first induction therapy or transplant after PR, relapse after CR or CRi or death due to any cause). Participants last known to be 1) alive and 2) without a DoR event, were censored at the date of the last disease assessment that verified lack of event.
Up to approximately 2 years from first dose
Overall Survival (OS)
Prazo: Up to approximately 2 years from first dose
OS was defined as the time from Cycle 1 Day 1 to date of death due to any cause. If death was not documented, censoring occurred at the date at which the participant was last known to be alive.
Up to approximately 2 years from first dose
Time to Remission for Participants Who Achieved CR or CRi
Prazo: Up to approximately 2 years from first dose
Time to remission was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic remission (CR or CRi) in participants achieving remission during study therapy.
Up to approximately 2 years from first dose
Time to Response for Participants Who Achieved CR/CRi or PR
Prazo: Up to approximately 2 years from first dose
Time to response was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic response (CR, CRi, or PR).
Up to approximately 2 years from first dose
Time to MRD Negativity for Participants Who Achieved CR or CRi
Prazo: Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
Time to MRD negativity was defined as the time from the date of first dose of study drug to the date of first documentation of MRD negativity.
Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
Duration of Follow-Up
Prazo: From first dose up to approximately 2 years
Duration of follow-up was defined as the time from the date of first dose of study drug to the date of last contact for participants known to be alive.
From first dose up to approximately 2 years
Percentage of Cluster of Differentiation-22 Positive (CD22+) Leukemic Blasts in Abnormal B Cells in Blood by Visit
Prazo: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
CD22+ leukemic blasts assessed in abnormal B cells from blood (data from central laboratories only).
Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
Percentage of CD22+ Leukemic Blasts in Abnormal B Cells in Bone Marrow by Visit
Prazo: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
CD22+ leukemic blasts assessed in abnormal B cells from bone marrow (data from central laboratories only).
Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
Messenger Ribonucleic Acid (mRNA) Gene Expression
Prazo: Predose and postdose on Days 1 and 15 of Cycle 1
Optional blood samples for pharmacogenomic parameters were collected during Cycle 1 prior to the start of the inotuzumab ozogamicin infusion (0 hours) and 1 hour post-dose (original Final Protocol and Protocol Amendments 1 and 2) or 3 hours post-dose (Protocol Amendments 3 and 4) on Day 1 and Day 15 from those participants who provided consent. Gene expression analysis of samples collected pre- and post-dosing was performed using 96-gene TaqMan® low density array cards to examine the concordance between clinical outcome and expression of genes such as those involved in DNA damage response, apoptosis, B-cell antigen expression, glutathione metabolism, drug transport and the phosphoinositide 3-kinase/mammalian target of rapamycin pathway. Expression for each gene was reported as a normalized value, 2^-change in (∆) threshold cycle (Ct), where ∆Ct is Ct^target gene minus Ct^reference genes, averaged.
Predose and postdose on Days 1 and 15 of Cycle 1

Colaboradores e Investigadores

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

Patrocinador

Pfizer

Colaboradores

UCB Pharma

Publicações e links úteis

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Publicações Gerais

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

1 de agosto de 2011

Conclusão Primária (Real)

1 de agosto de 2014

Conclusão do estudo (Real)

1 de janeiro de 2016

Datas de inscrição no estudo

Enviado pela primeira vez

11 de maio de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

27 de maio de 2011

Primeira postagem (Estimativa)

1 de junho de 2011

Atualizações de registro de estudo

Última Atualização Postada (Real)

13 de abril de 2017

Última atualização enviada que atendeu aos critérios de controle de qualidade

2 de março de 2017

Última verificação

1 de março de 2017

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • B1931010
  • 3129K6-1106 (Outro identificador: Alias Study Number)

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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