Étude du HMPL-760 Puls R-GemOx par rapport au Placebo Plus R-GemOx dans le DLBCL en rechute/réfractaire
Une étude de phase II randomisée et contrôlée pour évaluer l'efficacité, l'innocuité et la pharmacocinétique du HMPL-760 Plus R-GemOx par rapport au Placebo Plus R-GemOx chez les patients atteints de lymphome diffus à grandes cellules B en rechute/réfractaire (DLBCL R/R)
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).
Aperçu de l'étude
Statut
Les conditions
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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Fujian
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Fuzhou, Fujian, Chine
- Fujian Medical University Union Hospital
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Guangdong
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Guangzhou, Guangdong, Chine
- Sun Yat-sen University Cancer Center
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Guangxi
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Nanning, Guangxi, Chine
- Guangxi Medical University Cancer Hospital
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Hebei
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Wuhan, Hebei, Chine
- Wuhan Union Hospital of China
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Heilongjiang
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Harbin, Heilongjiang, Chine
- Harbin Medical University Cancer Hospital
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Harbin, Heilongjiang, Chine
- Harbin First Hospital
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Henan
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Zhengzhou, Henan, Chine
- Henan Cancer Hospital
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Zhengzhou, Henan, Chine
- The First Affiliated Hospital of Zhengzhou University
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Hunan
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Changsha, Hunan, Chine
- Hunan Cancer Hospital
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Jiangxi
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Nanchang, Jiangxi, Chine
- Jiangxi Cancer Hospital
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Nanchang, Jiangxi, Chine
- The First Affiliated Hospital of Nanchang University
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Liaoning
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Shenyang, Liaoning, Chine
- Shengjing Hospital of China Medical University
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Shandong
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Jinan, Shandong, Chine
- Shandong Cancer Hospital & Institute
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Chine
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Sichuan
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Chengdu, Sichuan, Chine
- West China Hospital of Sichuan University
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Chine
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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;
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
Autres noms:
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|
Comparateur 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.
Autres noms:
HMPL-760 placebo planned dose 1 daily (QD) orally |
|
Expérimental: 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.
Autres noms:
HMPL-760 planned dose 2 daily (QD) orally |
|
Comparateur 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.
Autres noms:
HMPL-760 placebo planned dose 2 daily (QD) orally |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Progression-free survival (PFS)
Délai: Up to approximately 2 years
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Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
Up to approximately 2 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Objective Response Rate (ORR)
Délai: Up to approximately 2 years
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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
Délai: Up to approximately 2 years
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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)
Délai: 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)
Délai: 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)
Délai: Up to approximately 2 years
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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)
Délai: Up to approximately 2 years
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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
Délai: 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
Délai: At the end of Cycle 7 (each cycle is 21 days)
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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
Délai: At the end of Cycle 7 (each cycle is 21 days)
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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
Délai: At the end of Cycle 7 (each cycle is 21 days)
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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
Délai: 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
Délai: 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
Délai: 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)
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Biomarker assessment
Délai: 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
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Metabolite analysis of HMPL-760 in combination with R-GemOx
Délai: 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)
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Weili Zhao, Ruijin Hospital
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs
- Maladies du système immunitaire
- Tumeurs par type histologique
- Maladies lymphatiques
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Lymphome non hodgkinien
- Lymphome à cellules B
- Lymphome
- Maladies hémiques et lymphatiques
- Lymphome diffus à grandes cellules B
- Acides aminés, peptides et protéines
- Protéines
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Thérapeutique
- Voies d'administration du médicament
- Pharmacothérapie
- Anticorps, monoclonal
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Désoxycytidine
- Cytidine
- Nucléosides pyrimidine
- Pyrimidines
- Anticorps, monoclonal et murin
- Rituximab
- Gemcitabine
- Injections
Autres numéros d'identification d'étude
- 2024-760-00CH1
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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