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- Ensaio Clínico NCT00150462
Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies
A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies
Visão geral do estudo
Status
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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California
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Beverly Hills, California, Estados Unidos, 90211-1850
- Tower Cancer Research Foundation
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Florida
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Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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New York
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New York, New York, Estados Unidos, 10021
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10021
- Weil Medical College of Cornell University
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New York, New York, Estados Unidos, 10032
- Herbert Irving Comprehensive Cancer Center, Columbia University
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Written informed consent in accordance with federal, local, and institutional guidelines
- Males and females ≥18 years of age
Histologically confirmed diagnosis of one of the hematologic malignancies below:
- Multiple myeloma (MM)
- Non-Hodgkin's lymphoma (NHL)
- Waldenström's Macroglobulinemia (WM)
- Hodgkin's disease (HD)
- Subjects who are refractory or relapsed following at least two prior therapies
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
- Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of < 3.0 times the upper limit of normal
Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥ 1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³
- Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
- Subjects receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation
- An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault
- Serum creatinine ≤ 2.0 mg/dL
- Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
- Female subjects of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test. Male subjects must use an effective barrier method of contraception throughout the study and for three months following the last dose if sexually active with a female of child-bearing potential.
Exclusion Criteria:
- Female subjects who are pregnant or lactating
- Subjects who are transfusion dependent
- Subjects with NHL or HL who have received steroid therapy in the previous seven days
- Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
- Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
- For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
- Subjects who have received allogeneic stem cell transplant therapy
- Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
- Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
- Major surgery within three weeks before Day 1
- Congestive heart failure (CHF) (New York Heart Association class III to IV)
- Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Subjects who are known or suspected of having human immunodeficiency virus (HIV) infection or who are HIV seropositive
- Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid (RNA) or hepatitis B antigen
- Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer with stable prostate specific antigen (PSA) levels for three years
- Subjects with treatment-related myelodysplastic disorder
- Subjects with known brain metastasis (active central nervous system [CNS] disease only)
- Serious psychiatric or medical conditions that could interfere with treatment
- Participation in an investigational therapeutic study within one month prior to Day 1
- Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
- Concurrent therapy with approved or investigative anticancer therapeutics
- Subjects with previous hypersensitivity to bortezomib injection
- Subjects with contraindications to receiving allopurinol
- Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
- Subjects with known or suspected amyloidosis
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: CFZ 1.2 mg/m²
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 2.4 mg/m²
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 4.0 mg/m²
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 6.0 mg/m²
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 8.4 mg/m²
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 11.0 mg/m²
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 15.0 mg/m²
Participants received carfilzomib 115.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 20.0 mg/m²
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 27.0 mg/m²
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 20/27 mg/m²
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
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Administered as an IV bolus dose
Outros nomes:
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Experimental: CFZ 20/27 mg/m² + DEX
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e.
40 mg weekly).
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Administered as an IV bolus dose
Outros nomes:
Administered orally prior to carfilzomib
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Number of Participants With Dose-limiting Toxicities (DLTs)
Prazo: 28 days
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A DLT was defined as any of the following occurring in the first 28 days of study participation: Nonhematologic:
Hematologic:
Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0. |
28 days
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Maximum Observed Plasma Concentration of Carfilzomib (Cmax)
Prazo: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)
Prazo: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib
Prazo: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib
Prazo: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Best Clinical Response to Treatment
Prazo: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Disease response criteria for NHL were according to the International Working Group Criteria for Non-Hodgkin's Lymphoma. Disease response criteria for Multiple Myeloma were according to the European Group for Blood and Marrow Transplantation (EBMT). Disease response criteria for WM were according to the consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. The disease response criteria for Hodgkin's Lymphoma are defined as follows:
Best clinical response is the best response observed from the start of study treatment until disease progression or death. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Duration of Response
Prazo: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Duration of objective response is defined as the time from the date of first documented assessment of clinical response (confirmed or unconfirmed complete response, partial response, or minimal response) to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment. Median duration of response was calculated using the Kaplan-Meier method. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Time to Progression
Prazo: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Time to progressive disease is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease, plus one day. Participants without tumor progression were censored at the date of their last clinical response assessment. Median time to progression was calculated using the Kaplan-Meier method. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Progression-free Survival
Prazo: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Progression-free survival is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease or death, whichever comes first, plus one day.
Participants without tumor progression or death were censored at the date of their last valid clinical response assessment.
Median progression-free survival was calculated using the Kaplan-Meier method.
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From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças cardiovasculares
- Doenças Vasculares
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Doenças Linfáticas
- Distúrbios imunoproliferativos
- Neoplasias por local
- Doenças Hematológicas
- Distúrbios hemorrágicos
- Distúrbios hemostáticos
- Paraproteinemias
- Distúrbios das Proteínas Sanguíneas
- Neoplasias de Células Plasmáticas
- Linfoma
- Neoplasias Hematológicas
- Mieloma múltiplo
- Doença de Hodgkin
- Waldenstrom Macroglobulinemia
- Efeitos Fisiológicos das Drogas
- Agentes Autônomos
- Agentes do Sistema Nervoso Periférico
- Antiinflamatórios
- Agentes Antineoplásicos
- Antieméticos
- Agentes gastrointestinais
- Glicocorticóides
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Agentes Antineoplásicos Hormonais
- Dexametasona
Outros números de identificação do estudo
- PX-171-002
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 .
Ensaios clínicos em Carfilzomib
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University of NebraskaNational Cancer Institute (NCI); AmgenConcluídoLinfoma periférico de células T | Linfoma Anaplásico de Grandes Células | Linfoma angioimunoblástico de células T | Linfoma de células T/NK extranodal tipo nasal adulto | Leucemia/Linfoma Recorrente de Células T do AdultoEstados Unidos
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AmgenConcluídoMieloma múltiploEstados Unidos, Canadá
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Ajai ChariAmgenConcluídoMieloma Múltiplo Refratário | Mieloma Múltiplo RecidivanteEstados Unidos
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Ohio State University Comprehensive Cancer CenterAmgenConcluídoCâncer hematopoiético/linfóide | Linfoma linfocítico pequeno recorrente | Leucemia Linfocítica Crônica de Células B | Leucemia Prolinfocítica | Leucemia Linfocítica Crônica RefratáriaEstados Unidos
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Northwestern UniversityAmgenRescindidoTeste de escalonamento de dose de carfilzomibe com e sem romidepsina em linfoma cutâneo de células TLinfoma não Hodgkin cutâneo recorrente de células T | Micose Fungóide Recorrente/Síndrome de Sézary | Linfoma não Hodgkin cutâneo de células T estágio III | Linfoma não Hodgkin cutâneo de células T estágio IV | Linfoma não Hodgkin cutâneo de células T estágio I | Estágio IA Micose Fungoide/Síndrome... e outras condiçõesEstados Unidos
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OncotherapeuticsAmgenConcluídoMieloma múltiploEstados Unidos
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Oslo University HospitalUniversity Hospital of North Norway; Helse Stavanger HF; Haukeland University... e outros colaboradoresRecrutamentoMieloma múltiploNoruega
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Henrik GregersenNordic Myeloma Study GroupDesconhecidoMieloma múltiploFinlândia, Dinamarca, Suécia, Noruega, Lituânia
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University of NebraskaM.D. Anderson Cancer CenterRescindidoMieloma múltiplo | Mieloma Múltiplo Refratário | Mieloma Múltiplo Recidivante/RefratárioEstados Unidos
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Mayo ClinicNational Cancer Institute (NCI)RetiradoMieloma Múltiplo Estágio I | Mieloma Múltiplo Estágio II | Mieloma Múltiplo Estágio III | Mieloma Múltiplo RefratárioEstados Unidos