Studio di HMPL-760 Puls R-GemOx rispetto a Placebo Plus R-GemOx nel DLBCL recidivante/refrattario
Uno studio randomizzato e controllato di Fase II per valutare l'efficacia, la sicurezza e la farmacocinetica di HMPL-760 Plus R-GemOx rispetto a Placebo Plus R-GemOx in pazienti con linfoma diffuso a grandi cellule B recidivato/refrattario (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).
Panoramica dello studio
Stato
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Fujian
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Fuzhou, Fujian, Cina
- Fujian Medical University Union Hospital
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Guangdong
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Guangzhou, Guangdong, Cina
- Sun Yat-sen University Cancer Center
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Guangxi
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Nanning, Guangxi, Cina
- Guangxi Medical University Cancer Hospital
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Hebei
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Wuhan, Hebei, Cina
- Wuhan Union Hospital of China
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Heilongjiang
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Harbin, Heilongjiang, Cina
- Harbin Medical University Cancer Hospital
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Harbin, Heilongjiang, Cina
- Harbin First Hospital
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Henan
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Zhengzhou, Henan, Cina
- Henan Cancer Hospital
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Zhengzhou, Henan, Cina
- The First Affiliated Hospital of Zhengzhou University
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Hunan
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Changsha, Hunan, Cina
- Hunan Cancer Hospital
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Jiangxi
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Nanchang, Jiangxi, Cina
- Jiangxi Cancer Hospital
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Nanchang, Jiangxi, Cina
- The First Affiliated Hospital of Nanchang University
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Liaoning
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Shenyang, Liaoning, Cina
- Shengjing Hospital of China Medical University
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Shandong
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Jinan, Shandong, Cina
- Shandong Cancer Hospital & Institute
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Cina
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Sichuan
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Chengdu, Sichuan, Cina
- West China Hospital of Sichuan University
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Cina
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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;
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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.
Altri nomi:
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|
Comparatore 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.
Altri nomi:
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
Sperimentale: 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.
Altri nomi:
HMPL-760 planned dose 2 daily (QD) orally |
|
Comparatore 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.
Altri nomi:
HMPL-760 placebo planned dose 2 daily (QD) orally |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Progression-free survival (PFS)
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Objective Response Rate (ORR)
Lasso di tempo: 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
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Complete response (CR) rate
Lasso di tempo: 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
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Duration of response (DoR)
Lasso di tempo: Up to approximately 2 years
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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
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Clinical benefit rate (CBR)
Lasso di tempo: Up to approximately 2 years
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Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD). |
Up to approximately 2 years
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Time to response (TTR)
Lasso di tempo: 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
|
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Overall survival (OS)
Lasso di tempo: 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
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Safety Endpoints of adverse events
Lasso di tempo: Up to approximately 2 years
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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
|
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
|
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
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Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx
Lasso di tempo: 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)
|
Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Biomarker assessment
Lasso di tempo: 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
Lasso di tempo: 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)
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Weili Zhao, Ruijin Hospital
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Neoplasie
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Malattie linfatiche
- Malattie linfoproliferative
- Disturbi immunoproliferativi
- Linfoma non Hodgkin
- Linfoma, cellule B
- Linfoma
- Malattie emiche e linfatiche
- Linfoma, a grandi cellule B, diffuso
- Aminoacidi, peptidi e proteine
- Proteine
- Composti eterociclici, 1-anello
- Composti eterociclici
- Terapie
- Rotte della somministrazione di droga
- Terapia farmacologica
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Deossictidina
- Citidina
- Nucleosidi di pirimidina
- Pirimidine
- Anticorpi, monoclonali, derivati da murina
- Rituximab
- Gemcitabina
- Iniezioni
Altri numeri di identificazione dello studio
- 2024-760-00CH1
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