Estudo da eficácia e segurança do eltrombopag em pacientes com SMD de baixo risco e dependentes de transfusão de plaquetas
Um estudo clínico randomizado, duplo-cego, placebo-controlado, no Japão Local Fase II, comparando monoterapia com eltrombopag versus placebo em pacientes adultos com síndrome mielodisplásica (SMD) de baixo risco com dependência de transfusão de plaquetas
This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This is a randomized, double-blind, placebo-controlled, Japanese local phase II study to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk MDS (IPSS-R very low, low, intermediate risk with bone marrow blast count < 5% and cytogenetic very good, good or intermediate risk). Platelet transfusion dependence at baseline is defined as receiving platelet transfusion regularly with a frequency of 2 or more times within 4 weeks prior to randomization. Platelet transfusion should be performed for a patient with platelet counts < 20 X 10^9/L, or with hemorrhagic symptoms and platelet counts < 30 X 10^9/L.
The primary objective is to demonstrate superiority of eltrombopag versus placebo in terms of the proportion of participants who achieve platelet transfusion independence at Week 24.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Aomori, Japão, 0308553
- Novartis Investigative Site
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Chiba, Japão, 2600852
- Novartis Investigative Site
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Fukushima, Japão, 9601295
- Novartis Investigative Site
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Gifu, Japão, 5008513
- Novartis Investigative Site
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Kumamoto, Japão, 8600008
- Novartis Investigative Site
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Osaka, Japão, 5340021
- Novartis Investigative Site
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Yamagata, Japão, 9909585
- Novartis Investigative Site
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Chiba
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Narita, Chiba, Japão, 2868523
- Novartis Investigative Site
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Fukuoka
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Kurume, Fukuoka, Japão, 8308543
- Novartis Investigative Site
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Hiroshima
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Ohtake, Hiroshima, Japão, 7390696
- Novartis Investigative Site
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Hyōgo
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Nishinomiya, Hyōgo, Japão, 6638501
- Novartis Investigative Site
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Ishikawa-ken
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Kanazawa, Ishikawa-ken, Japão, 9208530
- Novartis Investigative Site
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Kanagawa
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Isehara, Kanagawa, Japão, 2591193
- Novartis Investigative Site
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Yokohama, Kanagawa, Japão, 2210855
- Novartis Investigative Site
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Miyagi
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Sendai, Miyagi, Japão, 9808574
- Novartis Investigative Site
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Nagasaki
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Nagasaki, Nagasaki, Japão, 8528501
- Novartis Investigative Site
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Osaka
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Sakai, Osaka, Japão, 5900197
- Novartis Investigative Site
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Tokyo
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Bunkyo-ku, Tokyo, Japão, 1138603
- Novartis Investigative Site
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tabashi City, Tokyo, Japão, 1738606
- Novartis Investigative Site
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Yamaguchi
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Shimonoseki, Yamaguchi, Japão, 7500061
- Novartis Investigative Site
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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:
- Patients diagnosed with MDS according to the WHO classification revised 4th edition by investigator assessment with one of the following prognostic risk categories, based on the International
Prognostic Scoring System (IPSS-R):
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very low (0-1.5)
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low (2-3)
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intermediate risks (3.5-4.5) All following criteria for prognostic variables per IPSS-R should be met.
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Bone marrow blast < 5% (per both investigator's assessment and central review)
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Cytogenetic very good, good or intermediate risk corresponding to IPSS-R
- Platelet transfusion dependence
- Refractory, intolerant to, or ineligible for MDS treatments
- Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1
Exclusion Criteria:
- Patients with a history of prior administration of eltrombopag, romiplostim, or other TPO-RA
- Therapy-related MDS per WHO classification revised 4th edition
- MDS/myeloproliferative neoplasms including chronic myelomonocytic leukaemia per the WHO classification revised 4th edition
- MDS with excess blasts (EB) per WHO classification revised 4th edition
- Known history of IPSS-R high or very high risk MDS
- Currently receiving treatments for MDS (e.g., HMA, cyclosporine A (CsA) or lenalidomide). Supportive treatment with erythropoiesis-stimulating agents (ESAs) or erythroid mutation agent in anemic patients or granulocyte-colony stimulating factor (G-CSF) in patients with severe neutropenia and recurrent infections is allowed if at stable dosage for 3 months prior to screening and continued at the same dosing/schedule until the optimal dose of eltrombopag has been established.
- Patients scheduled for hematopoietic stem cell transplantation
- Bone marrow fibrosis that leads to an inability to aspirate adequate bone marrow sample
- Known thrombophilic risk factors (except in cases where potential benefits of participating in the study outweighed potential risks of thromboembolic events (TEE), as determined by the investigator)
Other protocol-defined inclusion/exclusion criteria may apply.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Eltrombopag Arm
Participants randomized to a 1: 1 ratio will take eltrombopag. |
Eltrombopag comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)
Outros nomes:
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Comparador de Placebo: Placebo Arm
Participants randomized to a 1: 1 ratio will take Placebo. |
Placebo comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD) |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of participants who achieve platelet transfusion independence at Week 24
Prazo: Week 24
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Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count. |
Week 24
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Time to platelet transfusion independence
Prazo: Year 1, Year 2
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This is defined as time from the date of randomization to the first day of a platelet transfusion-free period lasting at least 8 weeks. |
Year 1, Year 2
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Duration of platelet transfusion independence
Prazo: Year 1, Year 2
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This is defined for participants who have achieved platelet transfusion independence only and will be calculated from the first date of platelet transfusion-free resulting in achievement of transfusion independence to the date before becoming platelet transfusion dependent. |
Year 1, Year 2
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Percentage of participants with platelet transfusion independence
Prazo: Year 1, Year 2
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Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count. |
Year 1, Year 2
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Percentage of participants with platelet transfusion frequency reduction at Week 24
Prazo: Week 24
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This is defined as a reduction by at least 50 percent during the 4 prior weeks as compared to the 4 weeks prior to randomization. |
Week 24
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Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))
Prazo: Week 24, Year 1, Year 2
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Platelet response is defined as HI-platelet per International Working Group criteria. |
Week 24, Year 1, Year 2
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Time to platelet response
Prazo: Week 24, Year 1, Year 2
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This is defined as time from the date of randomization to the first date of achieving the platelet response criteria per modified IWG criteria. |
Week 24, Year 1, Year 2
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Duration of platelet response
Prazo: Week 24, Year 1, Year 2
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This is defined for participants who have achieved platelet response and will be calculated from the first date of achieving the platelet response criteria to the date before loss of platelet response per modified IWG criteria. |
Week 24, Year 1, Year 2
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Percentage of hematologic improvement-erythroid and -neutrophil
Prazo: Week 24, Year 1, Year 2
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per modified IWG criteria at 24 weeks, Year 1 and 2 |
Week 24, Year 1, Year 2
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Percentage of participants with disease progression excluding relapse after HI
Prazo: Week 24, Year 1, Year 2
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This is with regards to blast counts for both investigator assessment and central review per modified IWG criteria. |
Week 24, Year 1, Year 2
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Percentage of participants with relapse after HI and transfusion independence
Prazo: Week 24, Year 1, Year 2
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The percentage of participants with relapse after HI and transfusion independence at Week 24, Year 1 and 2. |
Week 24, Year 1, Year 2
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Percentage of participants with progression to Acute myeloid leukemia (AML)
Prazo: Week 24, Year 1, Year 2
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This is defined as ≥ 20% blasts at Week 24, Year 1 and 2 for both investigator assessment and central review per WHO classification revised 4th edition. |
Week 24, Year 1, Year 2
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Leukemia free survival (LFS)
Prazo: Week 24, Year 1, Year 2
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This is defined as time from the date of randomization to progression to AML per WHO classification revised 4th edition of ≥ 20 percent blasts or death due to any cause for both investigator assessment and central review. |
Week 24, Year 1, Year 2
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Clinically significant bleeding events
Prazo: Week 24, Year 1, Year 2
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This is defined as ≥ grade 2 events as per WHO bleeding scale. |
Week 24, Year 1, Year 2
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Overall survival (OS)
Prazo: Week 24, Year 1, Year 2
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OS is defined as time from randomization to death due to any cause. |
Week 24, Year 1, Year 2
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Quality of Life measured using QLQ-C30
Prazo: Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.
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The changes from baseline to each visit where measured using QLQ-C30. EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Subject's responses to 28 questions about their physical functioning, disease symptoms, global health status and utilities are scored on a 4-point scale (1=Not at all to 4=Very much), a low score indicates a high / healthy level of functioning. And the responses to 2 questions about health-related QoL are scored on a 7-point scale (1=Very poor to 7=Excellent), a high score indicates a high / healthy level of functioning. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. |
Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.
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Pharmacokinetics (PK): Cmax
Prazo: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants. |
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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PK: Tmax
Prazo: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants. |
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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PK: AUC
Prazo: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants. |
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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Trough concentrations of eltrombopag at steady state
Prazo: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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at each dose level in all the participants |
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
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
Outros números de identificação do estudo
- CETB115L11201
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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