Estudo de HMPL-760 Puls R-GemOx versus Placebo Plus R-GemOx em DLBCL recidivante/refratário
Um estudo randomizado e controlado de fase II para avaliar a eficácia, segurança e farmacocinética de HMPL-760 Plus R-GemOx versus Placebo Plus R-GemOx em pacientes com linfoma difuso de grandes células B recidivante/refratário (R/R DLBCL)
The goal of this study is to evaluate the efficacy of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).
Visão geral do estudo
Status
Descrição detalhada
A Phase II Randomized, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 in Combination with R-GemOx versus Placebo in Combination with R-GemOx in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
-
-
Fujian
-
Fuzhou, Fujian, China
- Fujian Medical University Union Hospital
-
-
Guangdong
-
Guangzhou, Guangdong, China
- Sun Yat-sen University Cancer Center
-
-
Guangxi
-
Nanning, Guangxi, China
- Guangxi Medical University Cancer Hospital
-
-
Hebei
-
Wuhan, Hebei, China
- Wuhan Union Hospital of China
-
-
Heilongjiang
-
Harbin, Heilongjiang, China
- Harbin Medical University Cancer Hospital
-
Harbin, Heilongjiang, China
- Harbin First Hospital
-
-
Henan
-
Zhengzhou, Henan, China
- Henan Cancer Hospital
-
Zhengzhou, Henan, China
- The First Affiliated Hospital of Zhengzhou University
-
-
Hunan
-
Changsha, Hunan, China
- Hunan Cancer Hospital
-
-
Jiangxi
-
Nanchang, Jiangxi, China
- Jiangxi Cancer Hospital
-
Nanchang, Jiangxi, China
- The First Affiliated Hospital of Nanchang University
-
-
Liaoning
-
Shenyang, Liaoning, China
- Shengjing Hospital of China Medical University
-
-
Shandong
-
Jinan, Shandong, China
- Shandong Cancer Hospital & Institute
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, China
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
-
-
Sichuan
-
Chengdu, Sichuan, China
- West China Hospital of Sichuan University
-
-
Tianjin Municipality
-
Tianjin, Tianjin Municipality, China
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
- Age ≥18 years;
- Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2;
- Histopathologically confirmed diagnosis of DLBCL;
- The investigator judges that the patient's current condition requires further treatment;
- Patients should have at least one bi-dimensionally measurable lesion;
- Expected survival is more than 12 weeks;
Exclusion Criteria:
- Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
- Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
- Organ insufficiency;
- Currently known history of liver disease, including cirrhosis, alcoholic liver, known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV):
- History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
- Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
- Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
- Clinically significant active infection;
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen
Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
HMPL-760 planned dose 1 daily (QD) orally R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Outros nomes:
|
|
Comparador de Placebo: Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Outros nomes:
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
Experimental: Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Outros nomes:
HMPL-760 planned dose 2 daily (QD) orally |
|
Comparador de Placebo: Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen
Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle. |
R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.
Outros nomes:
HMPL-760 placebo planned dose 2 daily (QD) orally |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Progression-free survival (PFS)
Prazo: Up to approximately 2 years
|
Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Up to approximately 2 years
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Objective Response Rate (ORR)
Prazo: Up to approximately 2 years
|
Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator. |
Up to approximately 2 years
|
|
Complete response (CR) rate
Prazo: Up to approximately 2 years
|
Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator. |
Up to approximately 2 years
|
|
Duration of response (DoR)
Prazo: Up to approximately 2 years
|
For patients who reached complete response (CR) or partial response (PR), Duration of Response (DoR) is defined as the time from the first CR or PR until disease progression or death due to any cause, whichever occurs first, as assessed by investigator. |
Up to approximately 2 years
|
|
Clinical benefit rate (CBR)
Prazo: Up to approximately 2 years
|
Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). |
Up to approximately 2 years
|
|
Time to response (TTR)
Prazo: Up to approximately 2 years
|
Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR), as assessed by investigator. |
Up to approximately 2 years
|
|
Overall survival (OS)
Prazo: Up to approximately 2 years
|
Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Up to approximately 2 years
|
|
Safety Endpoints of adverse events
Prazo: Up to approximately 2 years
|
Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of serious adverse events (SAEs), incidence of TEAEs leading to permanent discontinuation, dose interruption, and dose reduction, and their correlation to study drug. The severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0). |
Up to approximately 2 years
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Trough plasma concentration (Ctrough) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Maximum observed concentration, occurring at time Tmax at steady-state (Cmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Time of maximum observed concentration at steady-state(Tmax,ss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
The partial area from dosing time to dosing time plus Tau at steady-state (AUCss) of drug |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Apparent clearance at steady-state (CLss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
|
|
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Apparent volume of distribution at steady-state (Vz,ss/F) of drug (if applicable) |
At the end of Cycle 7 (each cycle is 21 days)
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Biomarker assessment
Prazo: Up to approximately 2 years
|
To evaluate the correlation between potential biomarkers and the prognosis of patients treated with this regimen. Tumor tissue or blood samples will be examined to detect the gene expression of MYD88. |
Up to approximately 2 years
|
|
Metabolite analysis of HMPL-760 in combination with R-GemOx
Prazo: At the end of Cycle 7 (each cycle is 21 days)
|
Analysis metabolite of HMPL-760 in combination with R-GemOx |
At the end of Cycle 7 (each cycle is 21 days)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Weili Zhao, Ruijin Hospital
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
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 (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
Termos MeSH relevantes adicionais
- Neoplasias
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Doenças Linfáticas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Linfoma Não-Hodgkin
- Linfoma de Células B
- Linfoma
- Doenças hemic e linfáticas
- Linfoma de Células B Grandes Difuso
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Terapêutica
- Rotas de administração de medicamentos
- Terapia medicamentosa
- Anticorpos, monoclonais
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Desoxicitidina
- Citidina
- Nucleosídeos de pirimidina
- Pirimidinas
- Anticorpos, monoclonais, derivados de murinos
- Rituximabe
- Gemcitabina
- Injeções
Outros números de identificação do estudo
- 2024-760-00CH1
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
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 .